Objective: To investigate whether Golgi stress (GAS) is involved in diabetic cardiomyopathy (DCM) and whether myocardial protection of exogenous spermine is associated with regulation of GAS. Methods: Sixty Wistar rats were randomly divided into normal control group (Control), diabetic group (T1D, STZ 60 mg/kg intraperitoneal injection) and spermine group (T1D+Sp, spermine 5 mg/(kg·d) intraperitoneal injection) for 12 weeks. H9C2 rat cardiomyocytes were randomly divided into control group (Control, 10% FBS-DMEM culture), high glucose group (HG, 10% FBS-DMEM+40 mmol/L glucose) and spermine group (HG+Sp, 10% FBS-DMEM+40 mmol/L glucose+5 μmol/L spermine). Rat serum creatine kinase isoenzyme (CK-MB) and cardiac troponin T (cTnT) were detected by ELISA; Golgi protein GOLPH3, GM130 and Cleaved Caspase3 protein expressions were analyzed using Western blot; immunofluorescence was used to detect GOLPH3 cell localization. Results: In the animal model, compared with the normal group, myocardial ultrastructural damage was obvious,the blood glucose, the serum myocardial enzymes CK-MB and cTnT, the expressions of GOLPH3 and cleaved caspase3 were increased or up-regulated significantly,meanwhile, the body weight,the ejection fraction (EF) and the expression of GM130 were decreased or down-regulated markedly in the diabetic group. In the cell model, similar results were obtained. Immunofluorescence showed stress fragmentation of Golgi apparatus. Exogenous spermine treatment could significantly alleviate the above mentioned damages. Conclusion: Golgi stress occurs in diabetic cardiomyopathy (DCM), and myocardial protection of exogenous spermine is associated with a reduction in Golgi stress (GAS).

Objective: To investigate the role of calcium-sensing receptor (CaSR) in the decrease of cardiac function in type 2 diabetic rats. Methods: Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups. Rats in the diabetes group were fed with high-glucose and high-fat diet, and intraperitoneal injection of streptozocin (STZ,30 mg/kg) was conducted 4 weeks later to establish a type 2 diabetes model. Cardiac morphological changes were observed by HE staining, cardiac function was detected by echocardiography, and CaSR and PKC-αprotein expressions in cardiac tissue were detected by Western blot. Results: Compared with the control group, the myocardium of diabetic rats showed irregular contraction zone, decreased expression of CaSR protein, increased expression of PKC-α protein, decreased systolic and diastolic functions, and gradually worsened with the prolongation of the course of the disease. Conclusion: Hyperglycemia inhibits the expression of CaSR protein in myocardium of diabetic rats by activating PKC-α, which can cause intracellular calcium disorder and lead to decreased cardiac function.

Objective: To study the relationship between myocardial remodeling and endoplasmic reticulum stress and autophagy in rats with ischemic cardiomyopathy. Methods: Thirty-six male SD rats were divided into normal control group, sham-operated group and ischemic cardiomyopathy group (n=12). Echocardiography was performed before operation in three groups. Rats in sham-operated group closed their thoracic cavity without ligation of coronary artery after thoracotomy. The rats in ischemic cardiomyopathy group were closed their thoracic cavity after ligating of coronary artery for 20 minutes and recovered reperfusion. After operation for 4 weeks, rats in three groups were killed after taking echocardiography. The myocardial tissues were taken for HE staining and Masson staining to observe the pathological changes of myocardium and the expressions of glucose-regulated protein 78 (GRP78), microtubule-associated protein 1 light chain 3- I (LC3-I), microtubule-associated protein 1 light chain 3- II (LC3-II), Bcl-2 interacting protein (Beclin-I) and the ratio of LC3-II/LC3-I were detected by Western blot. Results: Compared with normal group and sham-operated group, ischemic cardiomyopathy rats had significant differences in echocardiography and myocardial pathology; the myocardial array was disordered, myocardial fibrosis was increased, mitochondrial vacuolation was serious. Mean while, the expressions of GRP78, LC3-I, LC3-II, Beclin-I and LC3-II/LC3-I ratio had significant changes. Conclusion: Autophagy and endoplasmic reticulum stress may play important roles in myocardial remodeling in rats with ischemic cardiomyopathy.

Objective: To study the effects of hypericum perforatum extract (HPE) on myocardial fibrosis of the experimental autoimmune myocarditis (MFEAM) in mice. Methods: MFEAM model of immunosuppressive mouse was established by porcine cardiac myosin. The mice in the MFEAM model group were randomly divided into: MFEAM model group (n=14), HPE 100 mg/kg group (n=13), HPE 40 mg/kg group (n=13) and captopril (Cap) 50 mg/kg control group (n=13). Drug in each group was dissolved in 0.4 ml of physiological saline each time, and administered by intragastric administration twice a day for 60 days; the normal control group (n=10) and the MFEAM model group was given normal saline at the same volume and course of treatment as above described way. The ratio of heart weight and spleen weight to body weight were calculated, the general conditions of mice were observed. The contents of procollagen I N-terminal peptide(PINP), procollagen III N-terminal peptide (PIIINP) and TGF-β1 in serum of mice were detected. The degree of myocardial fibrosis (MF) and collagen volume fraction (CVF)were measured under the microscope by Masson staining. The protein expression of TGF-β1 was detected by Western blot. Results: The serum levels of TGF-β1, PINP and PIIINP in the model group were higher than those in the normal group significantly (P＜0.05 or P＜0.01). Meanwhile , the levels of MF and CVF were increased, and the protein expression of myocardial TGF-β1 was up-regulated. However, the serum levels of PINP, PIIINP and TGF-β1 in HPE40 mg/kg, HPE 100 mg/kg and Cap treated-groups were decreased significantly. HPE and Cap could improve or decrease the MF level and CVF of the MFEAM model mice, and down-regulated the expression of TGF-β1 protein in different degrees. Compared with the MFEAM model group, the difference was significant (P＜0.05 or P＜0.01).Conclusion: HPE has a therapeutic effect on MF, which may be related to its reduction of collagen deposition and inhibition of TGF-β1 signaling pathway.

Objective: To investigate the effects of hypoxia on the expressions of high mobility group box-1(HMGB1), HMGB1 receptors and inflammatory factors in human pulmonary artery smooth muscle cell( HPASMC) and human pulmonary artery endothelial cells (HPAEC).The effects of HMGB1 on the proliferation and migration activity of the two kinds of cells were detected. Methods: HPASMC and HPAEC were cultured under hypoxic conditions (Hypoxia at 1% oxygen, Hypoxia group) and normoxic conditions(Control group) . The mRNA levels of HMGB1, Toll-like receptors 2,4,9 (TLR2 , TLR4, TLR9), the receptor of advanced glycation end products(RAGE) , CD24 and IL-6 ,TNF-α,CXCL8 were detected by real-time PCR. Cell proliferation was measured by MTS. Cell migration was analysed by wound healing test. Results: Compared with control group, the expressions of HMGB1 mRNA and RAGE mRNA in both HPASMC and HPAEC were increased significantly (P＜0.05 and 0.01). Meanwhile, the expressions of CD24 mRNA in HPAEC and IL-6 mRNA in HPASMC of hypoxia group were increased significantly (P＜0.05). MTS results showed that HMGB1 inhibited the proliferation of HPAEC at 345 pmol/L significantly (P＜0.01). HMGB1 had no effect on the proliferation of HPASMC. Wound healing test showed that HMGB1 had no significant effect on HPASMC and HPAEC. Conclusion: HMGB1 was produced by HPAEC and HPASMC induced by hypoxia. HMGB1 induces endothelial barrier dysfunction by inhibiting HPAEC proliferation. Hypoxia stimulates HPASMC to produce inflammatory cytokines.

Objective: To investigate the effects of apolipoprotein E (apoE) on the proliferation of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. Methods: Primary culture of mouse PASMCs was prepared from male C57BL/6 mouse pulmonary artery by the method of tissue block anchorage. PASMCs were divided into four groups: normoxia group, normoxia with apoE administration group, hypoxia group and hypoxia with apoE administration group. The proliferation of PASMCs was observed by EdU incorporation. The protein levels of apoE, proliferating cell nuclear antigen (PCNA), protein kinase C (PKC) and phosphorylated protein kinase C (p-PKC) were analyzed by Western blot.Results: The percentage of PASMCs proliferation of hypoxia group was significantly higher than that of normoxia group by 64.7% (P＜0.05), and the protein expression levels of PCNA and p-PKC of hypoxia group were up-regulated than those of normoxia group by 69.0% and 120.0%, while the protein expression of apoE was down-regulated by 51.0% (P＜0.05), respectively. The percentage of PASMCs proliferation of hypoxia with apoE administration group was significantly lower than that of hypoxia group by 19.6% (P＜0.05), and the protein expression levels of PCNA and p-PKC of hypoxia with apoE administration group were down-regulated than those of hypoxia group by 19.8% and 103.2% (P＜0.05), respectively. There was no significant difference among each group in the protein expression of PKC, nor do there any significant difference between normoxia group and hypoxia group in the protein expression of p-PKC (P＞0.05). Conclusion: ApoE can inhibit the proliferation of PASMCs induced by hypoxia, and the mechanism of its effect may be attributed to blocking PKC pathway.

Objective: To study the effects of Fomes officinalis Ames. polysaccharides(FOPS) on anti-fatigue and hypoxia tolerance in mice. Methods: Forty-eight mice were randomly divided into control group, low-dose, middle-dose and high-dose group of FOPS (100, 200, 400 mg/kg). All mice were orally administered by 0.20 ml/10 g, once a day for 21 consecutive days. The effects of different doses of FOPS on the loaded-swimming time, the content of serum urea nitrogen, the blood lactic acid, the hepatic glycogen and the muscle glycogen after exercise, the survival time under hypoxia at normal pressure and the maintenance time after decapitation were observed. Results: FOPS could significantly prolong the loaded-swimming time, decrease the contents of serum urea nitrogen , blood lactic acid and increase the contents of hepatic glycogen and muscle glycogen, significantly prolong the survival time under hypoxia and the maintenance time after decapitation comparing with the control group. Compared with the control group, FOPS could prolong the weight-bearing swimming time, anti-hypoxia survival time and respiratory maintenance time of mice after decapitation in a dose-dependent manner (P＜0.05 or 0.01). FOPS could decrease the contents of serum urea nitrogen and blood lactic acid, and increase the contents of hepatic glycogen and muscle glycogen in exercise mice, and most of them were significantly different (P＜0.05) or extremely significant (P＜0.01). Conclusion: FOPS has anti-fatigue effects and can improve hypoxia tolerance.

Objective: To investigate the effects of mitochondrial ATPase inhibitory factor 1 (Atpif1) on hemoglobin synthesis. Methods: Firstly, the K562 cells were divided into 2 groups, hypoxia-treated group and normoxic control group. The K562 cells in hypoxia-treated group were treated with 2% oxygen. The K562 cells in the two groups were collected after cultured for 24, 48 and 72 hours. The proliferation-inhibitory rates of cells were detected by CCK-8 assay. The apoptosis rates of K562 cells were analyzed by flow cytometry. The hemoglobin synthesis of K562 cells was induced by hemin. The gene expressions of Atpif1, Aladelta-aminolevulinate synthase 2 (Alas2) and nuclear factor kappa B (NF-κB) were detected by qRT-PCR. Then, the K562 cells were cultured in hypoxic incubator and divided into blank control group, negative control group and si-Atpif1 group. After sliencing Atpif1 gene, the hemoglobin synthesis and the levels of NF-κB and Alas2 were determined. Results: Compared with the normoxic control group, the proliferation activity of K562 cells was inhibited, the apoptosis rate was increased, and the hemoglobin synthesis was also increased in hypoxia-treated groups. The expressions of Atpif1, Alas2 and NF-κB mRNA of K562 cells were upregulated. Compared with blank control group and negative control group, the content of hemoglobin was decreased, and the levels of NF-κB and Alas2 mRNA were also decreased in si-Atpif1 group. Conclusion: Atpif1 gene is involved in the regulation of hemoglobin synthesis. Exploring its roles in the development of high altitude polycythemia (HAPC) can provide new ideas and therapeutic targets for the prevention and treatment of HAPC.

Objective: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human gastric cancer MKN45 cells and its mechanism and provide experimental basis for the prevention and treatment of gastric cancer with Traditional Chinese Medicine (TCM). Methods: MKN45 cells were pre-treated with DHM (0,10,20,30,40,50 μmol/L) for 24 and 48 hours respectively. Cell viability treated with different concentrations of DHM was detected by Cell Counting kit (CCK-8) assay, cell migration was measured by wound healing assay, and cell invasion was tested by Transwell assay. Cells were pre-treated with DHM or co-treated with c-Jun N-terminal kinase (JNK) pathway inhibitor SP600125, then, the levels of migration- and invasion-related proteins were tested by Western blot. Results: DHM concentration-dependently inhibited cell migration and invasion and downregulated matrix metalloprotein -2 (MMP-2) and phosphorylated JNK (pJNK) expression in MKN45 cells, followed by upregulation of E-cadherin and downregulation of Vimentin. Co-treatment with DHM and JNK inhibitor SP600125 further suppressed MMP-2 expression and cell invasion in MKN45 cells, suggesting that DHM inhibited MKN45 cells metastasis through JNK/MMP-2 pathway. Conclusion: DHM can inhibit cell migration and invasion in human gastric cancer MKN45 cells through downregulating MMP-2 expression via JNK signaling pathway and reverse epithelial-mesenchymal transition (EMT), implying that DHM could have the potential to serve as an anti-metastatic agent for treating gastric cancer.

Objective: To investigate the effects of metformin (Met) on middle-aged male mice aging induced by D-galactose. Methods: Fifty nine-month-old male ICR mice were fed in SPF experimental environment and fed freely with water. Subsequently, the mice were randomly divided into 5 groups(n=10): control group, model group, metformin low, medium and high dose groups(Met 50 mg/kg, Met 100 mg/kg, Met 200 mg/kg). The mice in different doses of Met group and model group were subcutaneously injected with D-galactose 100 mg/kg at the back of neck to induce senescence every day. At the same time, the mice were respectively treated with Met (50, 100, 200 mg/kg) or NS of equal volume by gavage. The control group was injected and gavage with equal volume NS. All treatments lasted for 8 weeks. During the study, the general condition, body weight, blood glucose,the activities of superoxide dismutase (SOD) and malonic dialdehyde (MDA) in serum and liver tissue of each mouse were tested, learning and memory ability were measured by Mirris water maze test, HE staining was used to observe the pathology of hippocampus in the mice. Results: Met 200 mg/kg per day could reduce body weight (P＜0.05). Met intervention had no effect on normal fasting blood glucose in model rats. Compared with model group, the daily dose of Met 50, 100, 200 mg/kg could significantly increase SOD activity in serum and liver tissues of model mice (P＜0.05) and decrease MDA content in serum of model mice (P＜0.05), and improve most of the indicators of learning and memory ability of Morris water maze test (P＜0.05). HE staining showed that the neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus. Met intervention has dose-dependent effects on most indicators. Conclusion: Long-term treatment of Met can delay the aging process of middle-aged male mice induced by D-galactose, which may be related to reducing the weight of mice and enhancing the body's antioxidant level.

Objective: To observe the effects of different doses of acetyl-L-carnitine (ALC) on hindlimb motor function and spinal cord tissue structure in rats with spinal cord injury. The study will provide theoretical and experimental evidences for acetyl-L-carnitine's clinical treatment.Methods: Fifty-five SD rats aged 8-10 weeks were randomly divided into high, medium and low-dose drug intervention (SCI + ALC) group, injury group (SCI) and sham group for behavioral evaluation, MAD and SOD detection, as well as HPLC detection and HE staining. BBB scores and Rivlin experiments were performed to evaluate hindlimb motor function in each group. The morphology and structure of spinal cord tissue was detected by HE staining. Another 9 rats were randomly divided into Sham group, SCI group and ALC group for TUMEL detection of apoptosis. Results: The BBB scores of the high, medium, and low dose SCI+ALC groups were significantly higher than those in the SCI group. The medium and high-dose ALC groups had significant differences (P＜0.01), and the hindlimb motor function was significantly improved in rats. The maximum tilt angle of the Rivlin experiment was observed. The SCI+ALC group had a significantly increased angle compared with the SCI group (P＜0.05), the medium and high-dose ALC group had a significant difference (P＜0.01). Compared with the SCI group, the tissue structure of ALC high-dose group was improved significantly, the number of inflammatory cells and red blood cells was decreased, and the nucleolus of the nerve cells was unclear. The SOD activity of the SCI+ALC group was significantly higher than that of the SCI group, while the MDA content was significantly decreased(P＜0.05), the middle and high dose ALC groups were significantly different (P＜0.01). HPLC chromatogram showed that the SCI+ALC fresh serum sample and the ALC standard solution had the same absorption spectrum at 260 nm, while the Sham group and SCI group serum samples did not show spectral values there, which indicated that the same substance as the standard existed in the sample of SCI+ALC group. TUNEL staining showed that the apoptosis signal was occasionally seen in the sham group, and the apoptosis signal was significantly decreased in the ALC high-dose group compared with the SCI group(P＜0.05). Conclusion: ALC can promote the recovery of hindlimb motor function in rats with spinal cord injury, inhibit oxidative stress and apoptosis, and repair the damaged spinal cord tissue.

Objective: To investigate the effects of moxibustion on the structure and function of blood-brain barrier in Alzheimer's disease (AD) model rats. Methods: Forty-eight SD rats were randomly divided into 4 groups: normal control group, sham operation group, model group, moxibustion group. Model group and moxibustion group rats were injected with aggregated Aβ_25-35 by bilateral hippocampus. In the rat model, the sham-operated group was injected with the same amount of normal saline in the bilateral hippocampus, and the normal group was not treated. After successful modeling, the moxibustion treatment was given at 2～3 cm above the “Baihui”, “Shenshu” and “Yintang” points of the moxibustion group rats, each time for 10 min, once a day, continuous treatment for 21 d. The Morris water maze test was used to evaluate the learning and memory ability of rats in each group. The Evans blue method was used to detect the permeability of blood-brain barrier. The ultrastructure of blood-brain barrier was observed under electron microscope. The matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) positive cells in hippocampus were detected by immunohistochemistry. Results: Compared with the sham operation group, the escape latency was significantly increased (P＜0.01), and the space exploration time was decreased (P＜0.01), the learning and memory function in model group was impaired seriously, the Evans blue content in the brain was increased significantly (P＜0.01), the perivascular edema became larger, and the blood-brain barrier structure function was impaired. At the same time, the positive expressions of MMP-2 and MMP-9 in hippocampus were increased significantly (P＜0.01). Compared with model group, the learning and memory ability in moxibustion group rats was enhanced (P＜ 0.05), the content of Evans blue in the brain was decreased (P＜0.05), the degree of perivascular edema was reduced, and the damage of blood-brain barrier was improved. Positive expressions of MMP-2 and MMP-9 in hippocampus were decreased (P＜0.05 or P＜ 0.01). Conclusion: Moxibustion can decrease the expressions of MMP-2 and MMP-9, and reduce the damage of the structure and function of blood-brain barrier, thereby improving the learning and memory ability of AD model rats, and exerting therapeutic effects.

Objective: To investigate the anti-ulcerative colitis mechanism of resveratrol through regulation of Wnt/β-catenin signaling pathway. Methods: ①The experiment of ulcerative colitis induced by dextran sulfate sodium salt (DSS): 28 C57BL/6 mice were randomly divided into four groups including control group(n=7), DSS group(n=7), DSS+Resveratrol (DSS+Res) group(n=7) and Res group(n=7). The experiment lasted for 3 weeks. Ulcerative colitis of mice was induced by drinking DSS water and treated with resveratrol by intragastric administration. The mice were weighed daily and their activities and state of feces were recorded. After that, the mice were euthanized, the spleens were weighed, and the colonic length was measured.Hematoxylin-eosin staining (HE) was used to observe the pathological changes of the colon, and the expression of miR-31 in colonic tissue was detected by quantitative real-time PCR (qPCR). The expressions of β-catenin and Cyclin D1 were measured by Western blot. ②In vitro experiment: HCT 116 cells were treated with resveratrol at 10 mg/ml, the expressions of β-catenin, LDL receptor related protein-6 (LRP-6), frizzled-3 (FZD3) and c-Myc were detected. The expression of β-catenin was also detected in HCT 116 cells transfected with miRNA-31 mimic and miRNA-31 inhibitor. Results: ① The body weight was decreased in DSS group, the activity was decreased and blood stool appeared. The colonic length of mice was shortened, the spleen was enlarged and the tissue was damaged seriously in DSS group. While the above symptoms were improved after resveratrol treatment. ② Resveratrol inhibited the expressions of miRNA-31, β-catenin and CyclinD1 in ulcerative colitis mice, and also down-regulated the expressions of β-catenin, LRP-6, FZD3 and c-Myc in HCT 116 cells. After transfection of miRNA-31 inhibitor, the expression of β-catenin was decreased in HCT 116 cells. Conclusion: Resveratrol suppresses DSS induced colitis by down-regulation of Wnt signal pathway. The down-regulation of Wnt signal may be related to miRNA-31.

Objective: To study the effects of cold exposure on estrous cycle of female C57BL/6 mice. Methods: Twelve healthy female C57BL/6 mice were randomly divided into two groups: control group and cold exposure group, 6 in each group. Cold exposure group was exposed to 4℃, 4 h per day, while control group stayed in normal conditions. Vaginal smears were used to observe the estrous cycle. After 2 weeks, blood and uteri were collected from each mouse after anesthetized and weighted. Serum levels of estradiol(E2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(Prl) and progesterone(P) were determined by using mouse ELISA kits. The uterus and ovary pathological slices were prepared to observe the structural changes. Results: Compared with the control group, body weight gain showed no significant differences (P＞0.05). The cold group had significant lower coefficients of uterus and the diestrus phase was significantly increased after cold exposure (P＜0.01). Serum level of FSH in cold group was higher and Prl was lower significantly (P＜0.01). Pathological examination of uterus and ovary showed that uterine glands of cold group were expanded and the amount of follicles was decreased significantly. Conclusion: Cold exposure might increase mouse estrous cycle and affect their reproductive function.

Objective: To evaluate the effects of sustained military physical related activity on balance abilities and the role of visual system in it, so as to provide the basis for precise training. Methods: Fifty-four healthy males (age: 20.28±3.72 y, height: 173.21±5.67 cm; weight: 64.29±5.12 kg) were recruited in this experiment. Multiple military subjects were completed within 36 hours, and the workload was recorded (randomly select 11 people). After military activity, the balance abilities with opened eyes (54 people) and closed eyes (randomly selected 27 people) were evaluated. Results: In terms of internal load, the heart rates (HR), excess post-exercise oxygen consumption (EPOC) and training impulse (TRIMP) for all exercises were increased significantly in military activity compared with rest (P＜0.05). Regard to balance abilities, compared to the rest with eyes-opened, the sway path-total (SPT), sway path-A-P ( SPAP ), sway path-M-L (SPML), sway V-total (SVT), sway V-A-P (SVAP), and sway V-M-L (SVML)after sustained military activity with eyes-opened were increased significantly (P＜0.05), while sway maximal amplitude-A-P (SMAAP), sway maximal amplitude-M-L (SMAML), and area of 100% ellipse (AE) had no significant changes; Compared to the rest, all indicators after the military activity with eyes-closed were significantly increased (P＜0.05). So vision could control the amplitude and area after the military activity. Conclusion: Sustained military related activity can damage the balance ability. After sustained military activity, the degree of damage of the balance ability in the closed-eyes is greater than that of the open-eyes, the amplitude and range of the center of gravity are increased, indicates that the visual system plays major role in controlling attitude stability.

Objective: To investigate the protective effects of curcumin on bile duct ligation(BDL)-induced liver cholestasis in mice, so as to provide a new treatment strategy for liver fibrosis. Methods: Forty-two healthy adult male BALB/c mice were randomly divided into sham group (n =6), sham+curcumin group (n=6), BDL treatment group (n=10), BDL+curcumin group(n=10), BDL+curcumin+ZnPP group (n=10). Seven days after BDL operation, the sham operation + curcumin group and the BDL+ curcumin group were treated with curcumin at the dose of 30 mg/kg by intraperitoneal injection once a day for 7 days.The mice in BDL+ curcumin +ZnPP group were treated with curcumin (30 mg/kg) and ZnPP (50 μmol/kg) by intraperitoneal injection once a day for 7 days. For the sham group and the BDL group, mice were treated with equal-volume saline daily by intraperitoneal injection. After 14 days of BDL, the plasma and liver tissues were collected, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The pathological changes of liver tissue and liver fibrosis were observed, and the protein expression of HO-1 in liver tissue was detected. Results: Compared with the sham group, mice in the BDL group had enlarged liver gallbladder and the serum levels of ALT and AST were increased significantly (P＜0.05). Meanwhile, the results of Sirius red staining and qRT-PCR of pro-fibrosis related genes showed collagen deposition in the liver, and immunohistochemistry of macrophages and neutrophils showed inflammatory cell infiltration in the liver. Compared with the BDL group, the serum levels of ALT and AST in the curcumin treatment group were decreased significantly (P＜0.05), collagen deposition and inflammatory cell infiltration were improved, and HO-1 expression was increased (P＜0.05) after curcumin treatement. In the curcumin treatment group, the protective effect of curcumin on liver injury could be reversed by HO-1 active inhibitor ZnPP. Conclusion: Curcumin can improve liver inflammation and fibrosis caused by BDL, and this protective effect is related to the regulation of HO-1 activity by curcumin.

Objective: To investigate the expression changes of miRNAs (miR199a-5P, miR206, miR133a-3P, miR499-5P) in rat model of cardiac hypertrophy induced by isoproterenol (ISO), and to explore the main signal pathways and molecular mechanisms which related to that with the way of bioinformatics. Methods: Sixteen SD male rats were randomly divided into two groups: control group and ISO model group. The rats in model group were treated with ISO (1 mg/kg) to induce cardiac hypertrophy, the rats in control group were treated with the same amount of saline, and all were injected subcutaneously at the back. After 10 days of continuous administration, interventricular septal thickness at diastole (IVSd), left ventricular posterior wall thickness at diastole (LVPWd) , left ventricular end-diastolic diameter(LVDd), and systolic function (EF%) were measured by echocardiography. Heart weight (HW) and rat body weight (BW) were weighed, and heart/body weight ratio (HW/BW) was calculated. Myocardial tissues were stained with HE, and myocardial cell surface area was measured by Image J analysis software; RT-qPCR was used to detect the expressions of 4 miRNAs in rat myocardial tissues. Targetscan, miRDB and miRwalk databases were used to predict the possible target genes of four kinds of miRNAs in rats, and FunRich software was used to analyze and predict the signal pathways related to the target genes. Results: Compared with the control group, the IVSd and LVPWd in the model group were thickened, the LV was increased, and the EF% was decreased significantly. The HW and HW/BW were increased. The myocardial cell volume in the model group was increased significantly, the arrangement was disordered, and the cell surface area was increased; the expressions of miR199a-5P and miR206 in the model group were up-regulated by RT-qPCR (P＜0.05); the expressions of miR133a-3P and miR499-5P were down-regulated (P＜0.05). Predicted by bioinformatics application, related signal pathways which target genes of 4 miRNAs maybe involved in cardiac hypertrophy mainly are: VEGF/VEGFR signal pathway, ErbB receptor signal pathway and other signal pathways. Conclusion: ISO-induced cardiac hypertrophy leads to changes in miRNA expression, and bioinformatics predicts related target genes of four miRNAs involved in cardiac hypertrophy and their major signaling pathways. These studies will provide new ideas for the regulation of cardiac hypertrophy and its prevention and treatment measures.