Objective: To investigate the effect of Iptakalim (Ipt) preventing injury of endothelial microvesicles (EMVs) derived from hypoxia/reoxygenation (H/R)-treated HUVECs on the relaxation of rat thoracic aortic rings and explore the underlying mechanism. Methods: H/R injury model was established to release H/R-EMVs from HUVECs. H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. H/R-EMVs were characterized by using Transmission Electron Microscope (TEM). Thoracic aortic rings of rats were incubated with 10^-7-10^-3 mol/L Ipt and co-cultured with 10 μg/ml H/R-EMVs for 4 hours, and their endothelium-dependent relaxation in response to acetylcholine (ACh) was recorded in vitro. The nitric oxide (NO) production of ACh-treated rat thoracic aortic rings was measured by using Griess reagent. The expression of endothelial NO synthase (eNOS), phosphorylated eNOS (p-eNOS, Ser-1177), serine/threonine kinas (Akt) and phosphorylated Akt (p-Akt, Ser-473) in the thoracic aortic rings of rats was detected by Western blotting. Results: H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation. The isolated H/R-EMVs subjected to TEM revealed small, rounded vesicles (100-1 000 nm) surrounded by a membrane. H/R-EMVs impaired relaxation induced by ACh of rat thoracic aortic rings significantly. Compared with H/R-EMVs treatment individually, relaxation and NO production of rat thoracic aortic rings were increased by Ipt treatment in a concentration-dependent manner (P<0.05, P<0.01). The expression of total eNOS (t-eNOS) and total Akt (t-Akt) was not affected by Ipt or H/R-EMVs. However, the expression of p-eNOS and p-Akt increased after treated with Ipt (P<0.01). Conclusion: Based on H/R-EMVs treatment, ACh induced endothelium-dependent relaxation of rat thoracic aortic rings was ameliorated by Ipt in a concentration-dependent manner. The mechanisms involved the increase in NO production, p-eNOS and p-Akt expression.

Objective: The purpose of this study was to investigate the effects of desensitized nicotinic receptors (nAChRs) on striatal dopaminergic system in the hemiparkinsonian rats treated with 6-hydroxydopamine (6-OHDA). Methods: We examined the effects of desensitized nAChRs on the levels of dopamine (DA) and its metabolites, mRNA expression of dopamine receptor D1,D2 and monoamine oxidase B (MAO-B) in the striatum of 6-OHDA-lesioned rats using high-performance liquid chromatography and reverse transcription-polymerase chain reaction. Results: The results showed that nAChRs desensitization following repeated nicotine stimulation could reverse significantly the decrease of striatal DA and its metabolites levels and the increase in DA turnover in lesioned side striatum of hemiparkinsonian rats. Dopamine D1 receptor mRNA expression increased significantly, whereas dopamine D2 receptor mRNA expression remained unchanged in lesioned side striatum of nicotine-treated rats compared to 6-OHDA-lesioned rats when nAChRs were desensitized. Meanwhile, nicotine-treated rats displayed a significant decrease in MAO-B mRNA expression in lesioned side striatum compared to 6-OHDA-lesioned rats after nAChRs desensitization. Conclusion: These results suggest that nAChRs desensitization could promote DA level, upregulate dopamine D1 receptor expression and downregulate MAO-B expression in striatum of hemiparkinsonian rats.

Objective: Vascular tone had shown the potential susceptibility to acute mountain sickness (AMS), however the detailed tendency has not been studied. Methods: Vascular tone, SpO₂ and Rate pressure product (RPP) were studied in seventeen healthy subjects before and after rapid ascent from sea level to 3658 m. Human acute mountain sickness was evaluated by the Lake Louise Score (LLS). Results: Nine of the seventeen participants were diagnosed with AMS. On initial exposure, there was a significant decrease in vascular tone between subjects with and without AMS. Significance was also found in the decrease of SpO₂ before and after rapid ascent but the differences between subjects with and without AMS did not reach significance during the initial phase. Conclusions:Vascular tone on initial exposure in response to rapid ascent is a possible sign of susceptibility to AMS. Conclusion: measurement of vascular tone using a wearable sensor throughout the acute phase response will provide numerical values of pathophysiology throughout the development of AMS.

Objective: The aim of this work is to determine whether the angiotensin converting enzyme (ACE) I/D (insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease (CHD) in the Qinghai Han Chinese. Methods: This study enrolled 59 CHD patients and 193 CHD controls from Qinghai Cardiovascular Diseases Vocational Hospital. Blood samples were collected from each of the patient and control groups. The ACE-I/D polymorphism was detected by polymerase chain reaction (PCR). Results: The genotype frequencies of ACE-I/D for Ⅱ, ID, DD in patients and controls were 0.475, 0.441, 0.085 and 0.430, 0.446, 0.124, respectively. The allelic frequencies of I and D were 0.650, 0.350 and 0.695, 0.305, respectively. The OR of ID, DD and D alleles relative to Ⅱ for CHD was 1.116 (0.604-2.060), 1.619 (0.564-4.648) and 1.211 (0.777-1.889). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between the patient and control groups. Conclusion: There is no relation between ACE-I/D polymorphism and CHD in current Qinghai Han Chinese.

Objective: To observe the influence of heterogeneity on sleep-wake architecture in single-prolonged stress (SPS) animal model. Methods: SPS rats were subdivided into low responders (LR) and high responders (HR) based on their freezing responses to a novel environment. Sleeping time (ST), awakening numbers (AN), brief awakening numbers (bAN) and frequency distribution of sleep bouts were used as observing indicators, single factor variance analysis combined with Dunnett t test were used to compare the differences between control, exposure, LR and HR groups. Results: We found sleeping time was increased only in HR group. Moreover, awakening numbers and brief awakening number increased in exposure group and HR group during the light phase, but not in LR group. The number of sleep bouts for the ranges of 40-80s increased obviously in HR group, but not in exposure and LR group. In addition, there were significant correlation between sleep-related parameters and freezing in HR group, but not in LR group. Conclusion: Heterogeneity existed in SPS model in view of different sleep-wake architectures of SPS rats. Rats in HR group exactly mimicked the freezing response and sleep disorders of PTSD. So HR rats were more appropriate to be used as PTSD-like models, especially when studying sleep disorder in PTSD.

Objective: To study the effects of butylphthalide on bronchial asthma in guinea pigs, and investigate the involvement of endothelin. Methods: In guinea pigs, bronchial asthma was induced by injection of ovalbumin (OVA) and provoked by inhalation of OVA, and the effects of butylphthalide on asthma were evaluated through the changes it induced by OVA, pulmonary function, endothelin-1 (ET-1) contents and activity of endothelin converting enzyme-1 (ECE-1) in bronchoalveolar lavage fluid (BALF), serum and lung tissue, and the gene expression of ET-1 in lung tissue. Results: Butylphthalide significantly improved pulmonary function, lowered asthmatic behavior score, inhibited the activity of ECE-1, and reduced ET-1 gene expression level in lung tissue. Conclusion: Butylphthalide has an anti-asthma effect and the mechanisms involve inhibition of ECE-1 activity and lowering of ET-1geng expression.

Objective: To investigate the effect of creatine phosphate sodium (sodium phosphocreatine) on miRNA378, miRNA378^* and calumenin mRNA in adriamycin-injured suckling mouse myocardium. Methods: The suckling mouse myocardium of primary culture were randomly divided into control group, adriamycin group and treatment group. To identify the suckling mouse myocardium, Smooth muscle actin-α (α-SMA) was monitored by immunohistochemical method. Cardiac function was evaluated by transthoracic echocardiography. The mRNA change of miRNA378, miRNA378^* and calumenin mRNA were detected by quantitative real-time PCR. The expression of calumenin and GRP78 were identified by western blot. Results: Mitochondrial damage and vacuolization were found in adriamycin-induced suckling mouse myocardium compared with control group, while creatine phosphate sodium could reduce this phenomenon. Compared with the control group, the mRNA of miRNA378, miRNA378^* and calumenin in adriamycin group was reduced, while creatine phosphate sodium could increase this phenomenon. The expression of calumenin and GRP78 were decreased after adriamycin treatment in suckling mouse myocardiums, creatine phosphate sodium increased the expression of calumenin and GRP78. Conclusion: The results of this experiment might be closely related to the effects of that creatine phosphate sodium reduced the pathological mechanism of suckling mouse myocardium with myocarditis caused by adriamycin.

Objective: Acute mountain sickness (AMS) is a common condition in individuals who ascend to altitudes over 2 500 m. There is no measurements that can reliably predict or diagnose this condition. We therefore determined whether pulse oximetry data are associated with the development of AMS and can help diagnose AMS. Methods: We studied 58 young male undergraduates who traveled from Chongqing (300 m) to Lhasa (3 658 m) by train. We collected data on the ascent profiles and AMS symptoms based on the Lake Louise Score (LLS). The resting arterial oxygen saturation (R-SpO₂) and pulse rate were then measured using finger pulse oximetry. Results: In Golmud(2 800 m) and Tanggula(5 200 m), R-SpO₂ was significantly lower in the AMS group than in the group without AMS (P<0.05). However, upon arrival in Lhasa (3 658 m), the R-SpO₂ was higher in the AMS group than in the non-AMS group (P<0.05). In Tanggula, the change in the SpO₂ (CR-SpO₂) in the AMS group was higher than that in the non-AMS group (P<0.05). But in Lhasa, the CR-SpO₂ in the AMS group was lower than that in the non-AMS group (P<0.05). We also monitored heart rate (HR) throughout the study. In Xining(2 200 m) and Golmud, the HRs in the AMS group were higher than those in the non-AMS group. However, the HRs in the AMS group were lower than those in the non-AMS group in Tanggula and Lhasa. Conclusion: Based on the results of this study, the R-SpO₂ graph was not consistent. We can thus conclude that the utility of SpO₂ remains limited in the diagnosis of AMS. The results suggest that using pulse oximetry to diagnose AMS is not valuable in people ascending to Lhasa on the Qinghai-Tibet train.

Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm³, according to the tumor size all the animals were divided into the following four groups, eight rats in each group:solvent control group, gefitinib group (100 mg/kg), erlotinib group (50 mg/kg), afatinib group (20 mg/kg). Aniamals were treated with drugs by intragastric (i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: HuPrime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.

Objective: This study was conducted to examine the effects of aerobic exercise alone and aerobic exercise with resistance training on the quality of life in men over the age of 55 years with type 2 diabetes mellitus. Methods: A total of 54 participants were divided into the following three groups so that there were no significant differences in blood chemistry or physical ability indexes among the three groups:control, aerobic exercise, and aerobic exercise with resistance training. The latter two groups exercised for 24 weeks, while the control group performed no exercise. Blood chemistry levels and measures of physical ability in each group members were examined one day before and one day after the exercise regimens. Results: Compared with those before the study, blood glucose, glycated hemoglobin, triglycerides, cholesterol, and low-density lipoprotein levels as well as vital capacity, reaction time, sit-and-reach ability, and balancing while standing on one leg with closed eyes were significantly improved in the aerobic exercise only group (P < 0.05). All these measures as well as high-density lipoprotein levels and grip, back, and leg strength were significantly improved in the combined aerobic and resistance training group (P < 0.05). By contrast, no significant differences before and after the experiment were found in any measure for the control group (P > 0.05). Conclusion: Although both aerobic exercise and aerobic exercise combined with resistance training for 24 weeks effectively improved the quality of life in patients with type 2 diabetes, the effect of the combined training was better than that of aerobic exercise alone. These results suggest that resistance training may be safely added to the rehabilitation training regimen of patients with type 2 diabetes mellitus.

Objective: The purpose of this study is to investigate the characteristic of microcirculation in healthy volunteers and patients with septic shock in both Xining (2 260 m) and Nanjing (10 m). Methods: A total of 62 cases, 33 healthy volunteers, 22 cases in Xining, (2 260 m above sea level) and 11 cases in Nanjing (10 m above sea level); and 29 septic shock, 13 cases in Xining and 16 cases in Nanjing were collected. The total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessel (PPV) and microcirculation flow index (MFI) of both healthy volunteers and septic shock had been investigated by using sidestream dark field (SDF). Analyzed and managed the image data by using AVA3.0 software. Results: In the healthy volunteers in Xining area (22 cases),the volume of TVD (15.59 ±2.58 mm/mm²), PVD (15.58 ±2.58 mm/mm²) and PPV(96.60% ±4.63%) were significant higher than the volume of TVD (10.0 ±2.10 mm/mm²), PVD (10.81 ±2.38 mm/mm²) and PPV (84.24% ±8.00%) of the volunteers (11 cases) in Nanjing (11 cases). But the MFI (2.17 ±0.31) of the healthy volunteers in the Xining was significant lower (P<0.05) than the MFI (3.21 ±0.34) in the healthy volunteers of Nanjing. In the septic shock group (13 cases) in the Xining, the volume of TVD (5.44 ±1.94 mm/mm²), PVD (4.18 ±1.61 mm/mm²), PPV (42.14%±5.38%) and MFI (1.05 ±0.32) compared with the volume of the healthy volunteers in Xining, the TVD (15.59 ±2.58 mm/mm²), PVD (5.58 ±2.58 mm/mm²), PPV (96.60% ±4.63%) and MFI (2.17 ±0.30) were significant lower (P<0.05). In the healthy volunteers compare with septic shock group in Nanjing area, the TVD(6.80±1.72 vs 10.00±2.10, P<0.05), PVD(5.86±1.58 vs10.81±2.38,P<0.05), PPV(45.42±4.86 vs 84.24±4.86, P<0.05), MFI(1.28±0.28 vs 3.21±0.34 P<0.05), there was significant decreased. In the septic shock group in the Xining compared with the septic shock in Nanjing, there was no significant difference. 10 of 13 patients with septic shock were survived in Xining. 13 of 16 patients with septic shock were survived in Nanjing. Conclusion: The changes of physiological and pathophysiological characteristic in microcirculation induced by hypoxia would be useful for clinical treatment of septic shock at high altitude.

Objective: To investigate the protective effect and possible mechanism of recombinant adiponectin on apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) induced by tert-butyl hydroperoxide (t-BHP). Methods: HUVECs were cultured in vitro and apoptosis was induced by t-BHP. On this basis, HUVECs were transfected with adenovirus carrying adiponectin prior to exposure to t-BHP, to further explore the protective effect of adiponectin on apoptosis induced by t-BHP. The percentage of cell viability was determined by MTT assay. The apoptotic rate was evaluated by fluorescence microsopic analysis with Hochest/PI staining. The protein levels of p-JNK, JNK and Caspase 3 were detected by Western blot. Results: Following t-BHP 100 μmol/L administration for 8 h, the ratio of apoptotic cells was increased. Western blot revealed that the protein levels of p-JNK and active caspase 3 were increased(P<0.01) compared to the control group. When cells were pretreated by adenovirus with adiponectin, the apoptosis rate and protein levels of p-JNK and active caspase 3 were decreased significantly(P<0.01). Conclusion: Continuous exposure to t-BHP induced apoptosis in HUVECs. Recombinant adiponectin protected HUVECs from apoptosis induced by t-BHP, which was correlated with the downregulation of p-JNK and active Caspase 3.

Objective: To investigate the changes of shock avoidance response in Y maze and the real-time local field potentials (LFPs) on hippocampal CA3 region in adolescent rats with high fat feeding. Methods: The juvenile rats of weaning 1 week were fed separately on basic feed (BF) and high fat diet (HFD) for 4 weeks until the puberty. Using the electric shock avoidance training method, the relevant parameters of reaching the learning standard of two groups of rats were recorded, and the LFPs of CA3 region in hippocampus were explored simultaneously by wireless telemetry. Results: Compared with the BF group, the body weight of HFD rats were increased significantly(P<0.05), the rats percentage of reaching the learning standard within 1 to 2 days and the various parameters of shock avoidance recorded in training were all superior to those of BF group rat,the LFP rhythm of bilateral hippocampal CA3 region appeared to the desynchronizd fast wave. The θ and γ1 rhythms of right hippocampal CA3 region shown synchronous increase, but there was no coupling formation in phase-amplitude of the θ and γ1 rhythms. Conclusion: From juvenile to adolescent with HFD intake, the adolescent rat gained an increase significantly in weight,but the ability of shock avoidance and the function of hippocampus-dependent spatial cognition in Y maze had not be expected decline.

Objective: To investigate the effects of the serotonergic nervous system on motor behaviors mediated by cerebellar fastigial nucleus (FN). Methods: In this experiment, the main methods are whole-cell patch clamp recording and Rota-rod test. Results: We found that the excitatory synaptic transmission was enhanced in the cerebella FN after blocking 5-hydroxytryptamine,(5-HT)receptor. Microinjection of 5-HT into FNs remarkably promoted motor performances on Rota-rod, which could be reversed by microinjection of 5-HT receptor antagonist SB224289. Conclusion: These results suggest that the 5-HT can suppress cerebellar FN excitatory synaptic transmission via 5-HT_1B receptors, thereby modulate the activity of cerebellar nuclear neurons circuitry, and subsequently influence the cerebellum-mediated ongoing motor balance and coordination.

Objective: To investigate the relationship between miRNA378, calumenin and endoplasmic reticulum stress in suckling mouse myocardium with myocarditis caused by adriamycin. Methods: The suckling mouse myocardium of primary culture were randomly divided into control group, adriamycin group, lentivirus infection miRNA378 over expression control group, lentivirus infection miRNA378 over expression group, lentivirus infection miRNA378 silence control group and lentivirus infection miRNA378 silence group. Firstly to identify the suckling mouse myocardium, α-SMA was monitored by immunohistochemical method, and secondly the ventricular myocytes were transfered by lentivirus plasmids. Then the expression change of miRNA378, calumenin and glucose regulated protein 78(GRP78) mRNA were detected by Quantitative Real-time PCR. Results: Compared with the adriamycin infection group, the expression of calumenin mRNA in lentivirus infection miRNA378 over expression group was increased(P<0.01), while the expression of GRP78 mRNA was reduced(P<0.01); Compared with the adriamycin infection group, the expressions of calumenin and GRP78 mRNA in lentivirus infection miRNA378 silence group did not change insignificantly. Conclusion: Adriamycin injection may cause expression of calumenin in suckling mouse myocardium with myocarditis reduced, which may lead to the endoplasmic reticulum stress. This effect is related with miRNA378.

Objective: To investigate the expressions of key proteins type IV collagen (CoIV), zonula occludens-1(ZO-1), α-smooth muscle actin(a-SMA) and the mechanisms of the structural injuries of the blood brain barrier in the hippocampus of diabetic rats with depression. Methods: After 14 days of high-fat diet, the rats were treated with streptozotocin (STZ, 38 mg/kg, iv). Then, the animals were randomly divided into 2 groups (n=15):the diabetic group and the diabetes mellitus with depression group. The normal rats were randomly divided into 2 groups(n=15):the control group and the depression group. Diabetic group and control group were kept in normal conditions. The diabetes mellitus with depression group and the depression group were treated with chronic unpredictable stress for 28 days. The levels of blood glucose were detected. The behavior changes of rats were evaluated by open-field test and Morris test. The blood brain barrier morphological changes were observed under the electron microscope. The expressions of CoIV, ZO-1 and a-SMA in rat hippocampal blood-brain barrier were detected by immunocytochemistry. Results: Compared with control group, the level of blood glucose was increased,the number of autonomic activity was decreased, the escape latencies were significantly longer in the Morris water maze test, as well as the space exploration times were shortened in the diabetes mellitus with depression group (P<0.05, P<0.01). The endothelial cells of the hippocampus were blurred, the capillary lumen was narrow, and the peripheral glial cells were edema, the expressions of ZO-1 and a-SMA were decreased(P <0.05), while the expression of CoIV was increased(P <0.05). Compared with diabetic group, the number of autonomic activity in the diabetes mellitus with depression group was significantly decreased (P<0.01), the escape latencies were longer (P<0.05), the blood brain barrier capillary lumen was more narrow and the glial cell terminal edema was more obvious, the expression of a-SMA was decreased(P<0.05). Conclusion: The abnormal expressions of ZO-1, CoIV and -SMA, key proteins in the hippocampal blood brain barrier, may be involved in the mechanisms of structural damages of the blood brain barrier in diabetes mellitus with depression.

Objective: To study the effects of extraction of Angelicae sinensis and Astragalus mongholicus (EAA) on the peritoneal structure, functions and transforming growth factor-β₁(TGF-β₁) expression in the chronic peritoneal failure rats. Methods: Fifty SD rats were randomly divided into normal control group, model control group, positive control group, high-dose and low-dose EAA group(n=10). The modeling rats were established by intraperitoneal injection(ip) 4.25% high-glucose peritoneal dialysate 100 ml/kg, lasted 40 d, and ip lipopolysaccharides (LPS) 5 mg/kg at 8^thd, 10^thd and 12^thd. At the same time, the rats were treated with the corresponding drugs. The body weight and general states, the levels of ultrafiltration volume, the parameters of peritoneal transport function, the changes of peritoneal morphology and the TGF-β₁ expression in parietal peritoneum of rats were observed. Results: EAA could increase the levels of ultrafiltration volume and improve the parameters of peritoneal transport function. The peritoneal thickness were decreased, and the TGF-β₁ expression in parietal peritoneum were also lowered significantly. Conclusion: EAA has some protective effects on the peritoneal structure and functions, and can inhibit TGF-β₁ expression.

Objective: To study the neuroprotective effects of a novel GIP/GLP-1 receptor dual agonist CI-1206 against Aβ1-42-induced impairments in spatial working memory and long term memory in mice. Methods: C57 mice, after receiving intracerebralventricular (i.c.v.) injection of Aβ1-42 and intraperitoneal injection of CI-1206, were divided into the following groups:saline+D-PBS, Aβ1-42+saline, CI-1206+D-PBS and Aβ1-42+CI-1206 group (n=12). Y maze spontaneous alternation of mice was tested to assess short term working memory, and Morris water maze task was used to assess long term reference memory. Results: ①The percentage of right alternation of mice in Aβ1-42+saline group was significantly decreased, while the percentage in Aβ1-42+CI-1206 group was significantly larger than that in Aβ1-42 alone group (P<0.05). ②In Morris water maze test, the escape latency of mice in Aβ1-42+saline group showed a significant increase, with a significant decline in swimming time in target quadrant. Treatment with CI-1206 significantly antagonized these detrimental effects induced by Aβ1-42. ③Aβ1-42 and CI-1206 did not affect the motor ability and vision of mice. Conclusion: I.C.V. administration of Aβ1-42 impaired the short term and long term spatial memory of mice, while CI-1206 could effectively antagonize the detrimental effects.

Objective: To investigate the effects of the Toll like receptor 4 (TLR4) -P38-JNK signaling pathway in the apoptosis of hippocampal neurons in rats and its mechanisms. And to provide new experimental evidences for the pathogenesis research, prevention and treatment of neurodegenerative diseases (ND). Methods: The hippocampal neurons derived from newborn rat were cultured for 7 d in vitro. The purity of hippocampal neurons was identified by immunofluorescence method. In order to activate or block the action of TLR4, the hippocampal neurons were pretreated with TLR4 ligand lipopolysaccharide (LPS) or TLR4 antibody. In the experiment 1, the hippocampal neurons were divided into normal control group, LPS group and TLR4 antibody+LPS group. The expressions of P-P38 and P-JNK were deteced by immunofluorescence. In the experiment 2, the hippocampal neurons were divided into 6 groups:normal control group, LPS group, TLR4 antibody +LPS group, SB202190(inhibitor P38)+LPS group, SP600125(inhibitor JNK)+LPS group, PD98059(inhibitor ERK)+LPS group. The cells in above mentioned groups were pretreated with TLR4 antibody, the inhibitors of P38, JNK or ERK for 2 h respectively. Then, all the six groups were stimulated by LPS for 24 h. The expressions of Bcl-2, Bax and Active-caspase-3 were detected by Western blot. The hippocampal neuronal apoptosis rate were tested with flow cytometry. Results: The expressions of P-P38 and P-JNK of hippocampal neurons in LPS group were higher than those in normal control group (P<0.01). Compared with LPS group, the expressions of P-P38 and P-JNK were decreased significantly in TLR4 antibody +LPS group (P<0.01). Compared with the normal control group, the expressions of Bcl-2/Bax were decreased, while the expression of Active-caspase-3 was increased in the hippocampal neurons after LPS stimulation (P<0.01). The apoptotic rate of hippocampal neurons was higher in LPS group than that in the control group (P<0.01). Compared with LPS group, the expressions of Bcl-2/Bax were increasd and the expression of Active-caspase-3 was decreased in TLR4 antibody+LPS group, SB202190+LPS group, and SP600125+LPS group. The apoptotic rate of hippocampal neurons was significantly lower than that in the LPS group (P<0.05, P<0.01). The cell apoptosis rate had no significant differences between PD98059+LPS group and LPS group. Conclusion: ①TLR4-mediated P38/JNK signaling pathway exists in hippocampal neurons. ②After TLR4 activation in hippocampal neurons, the expressions of P-P38 and P-JNK are up-regulated, the expressions of Bcl-2/Bax are decreased and the expression of Active-caspase-3 is increased, which promote apoptosis of hippocampal neurons. TLR4/P38/JNK signaling pathway is involved in apoptosis of hippocampal neurons.