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  • 中国应用生理学杂志
      2016年, 第32卷, 第6期 刊出日期:2016-11-28 上一期    下一期
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    研究论文
    Iptakalim ameliorates relaxation to acetylcholine in thoracic aortic rings impaired by microvesicles derived from hypoxia/reoxygenation-treated HUVECs
    Kun-wei ZHANG, Shao-xun WANG, Ye-yi LI, Su WEI, Man SHANG, Chao LIU, Miao LIU, Yi-lu WANG, Qian ZHU, Yan-na WU, Jun-qiu SONG, Yan-xia LIU
    中国应用生理学杂志. 2016, 32 (6): 481-486.   DOI: 10.13459/j.cnki.cjap.2016.06.001
    摘要   PDF (761KB)
    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.
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    Modulation by desensitized nicotinic receptors on metabolism of DA in striatum derived from the hemiparkinsonian model
    Fu-rong HAN, Hai WANG
    中国应用生理学杂志. 2016, 32 (6): 487-493.   DOI: 10.13459/j.cnki.cjap.2016.06.002
    摘要   PDF (590KB)
    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.
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    Identification of susceptibility to acute mountain sickness by detecting vascular tone using a photoplethysmographic sensor
    Xiao-min LUO, Lei WANG, Lei YANG
    中国应用生理学杂志. 2016, 32 (6): 494-498.   DOI: 10.13459/j.cnki.cjap.2016.06.003
    摘要   PDF (430KB)
    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.
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    Association study between the angiotensin converting enzyme gene insertion/deletion polymorphism and Qinghai Han Chinese with congenital heart disease
    Jing ZHAO, Lin LU, Yong-nian LIU, Zhan-hai SU, Ying-zhong YANG
    中国应用生理学杂志. 2016, 32 (6): 499-503.   DOI: 10.13459/j.cnki.cjap.2016.06.004
    摘要   PDF (350KB)
    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.
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    The influence of heterogeneity on the analysis of sleep-wake architecture in the single-prolonged stress rats
    Ying WANG, Hong-sheng BIAN, Hang ZHAO, Ting-li LI
    中国应用生理学杂志. 2016, 32 (6): 504-508.   DOI: 10.13459/j.cnki.cjap.2016.06.005
    摘要   PDF (387KB)
    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.
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    Effects of butylphthalide on bronchial asthma in guinea pigs and involvement of endothelin
    Zhi-wang WANG, Xiao-yan FU, Yuan REN, Hai-jing DUAN, Xue-feng LIU, Xiao-li CHENG
    中国应用生理学杂志. 2016, 32 (6): 509-513.   DOI: 10.13459/j.cnki.cjap.2016.06.006
    摘要   PDF (2077KB)
    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.
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    Effect of creatine phosphate sodium on miRNA378, miRNA378* and calumenin mRNA in adriamycin-injured cardiomyocytes
    Miao YU, Zhi-hui HE, Li-ying XUAN, Xiao-tong SHAN, Jie LONG, Jing-yi FENG, Yu WANG, Ming ZHAO
    中国应用生理学杂志. 2016, 32 (6): 514-518.   DOI: 10.13459/j.cnki.cjap.2016.06.007
    摘要   PDF (1571KB)
    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.
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    Changes in oxygen saturation can not help diagnose acute mountain sickness (AMS): ascending to Lhasa on the Qinghai-Tibet train
    Jun-bo AN, Hao-ran GU, Yu WU, Yong-jun LUO
    中国应用生理学杂志. 2016, 32 (6): 519-524.   DOI: 10.13459/j.cnki.cjap.2016.06.008
    摘要   PDF (711KB)
    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.
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    The efficacy of TKIs in treatment of human primary small cell lung cancer xenograft model in vivo
    Yu-hua ZHANG, Liang SUN, Bin LIU, Guo-qiang LI
    中国应用生理学杂志. 2016, 32 (6): 525-528.   DOI: 10.13459/j.cnki.cjap.2016.06.009
    摘要   PDF (396KB)
    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.
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    The therapeutic effect of aerobic exercise with resistance training in elderly men with type 2 diabetes mellitus
    Hai-guo LIU, Guo-zheng LI
    中国应用生理学杂志. 2016, 32 (6): 529-532.   DOI: 10.13459/j.cnki.cjap.2016.06.010
    摘要   PDF (319KB)
    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.
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    Changes of microcirculation in healthy volunteers and patients with septic shock in Xining
    Si-qing MA, Shao-hua PENG, Zong-zhao HE, Hao WANG, Jing-yuan XU, Hai-bo QIU, Xin-hui Li, Jun-ming LUO
    中国应用生理学杂志. 2016, 32 (6): 533-539.   DOI: 10.13459/j.cnki.cjap.2016.06.011
    摘要   PDF (611KB)
    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.
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    脂联素抑制t-BHP诱导的内皮细胞凋亡作用及其可能机制探讨
    吴莉, 刘鲁豫, 官滨斌, 王林曦, 刘小莺, 陈闽, 陈洲, 刘礼斌
    中国应用生理学杂志. 2016, 32 (6): 540-544.   DOI: 10.13459/j.cnki.cjap.2016.06.012
    摘要   PDF (2005KB)
    目的:探讨重组脂联素对第三丁基过氧化氢(t-BHP)诱导的人脐静脉内皮细胞(HUVECs)凋亡的影响及其相关的分子机制。方法:以HUVECs作为研究对象,给予t-BHP处理,模拟体外HUVECs氧化损伤细胞凋亡模型。在此基础上,用携带重组脂联素基因的腺病毒转染HUVECs,观察重组脂联素对t-BHP诱导的HUVECs凋亡的影响。用MTT法检测细胞增殖活力。Hochest/PI荧光染色检测细胞凋亡率。Western blot检测细胞凋亡相关蛋白p-JNK、JNK和Caspase 3表达水平的变化。结果:100 μmol/L的t-BHP作用8 h可诱导HUVECs发生凋亡。与对照组相比,t-BHP组p-JNK、active caspase 3表达增多(P<0.01)。HUVECs高表达重组脂联素基因后,可明显抑制t-BHP诱导的HUVECs凋亡(P<0.01),下调t-BHP诱导的p-JNK、active caspase 3表达。结论:持续t-BHP氧化损伤可诱导HUVECs发生凋亡。重组脂联素可有效抑制t-BHP诱导的HUVECs凋亡,其机制与p-JNK、active caspase 3的表达下调有关。
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    高脂饲养青春期大鼠电击回避反应和海马CA3区场电位的改变
    王丹丹, 王羽, 汪镜静, 陈颖, 叶政, 李晶, 李敏, 朱再满, 潘群皖
    中国应用生理学杂志. 2016, 32 (6): 545-549.   DOI: 10.13459/j.cnki.cjap.2016.06.013
    摘要   PDF (1422KB)
    目的:观察高脂饲养至青春期的大鼠对电击回避反应和海马CA3区实时局部场电位变化。方法:断乳1周幼鼠改用基础饲料和高脂饲料分别喂养4周至青春期,分为基础饲料组(BF组)和高脂饲料组(HFD组),Y型迷宫电击回避训练方法,记录2组大鼠电击回避达学会标准的相关参数,同时无线遥测大鼠达标时海马CA3区实时局部场电位。结果:与BF组大鼠比较,HFD组大鼠体重明显增加,Y型迷宫电击回避训练1~2 d大鼠达标百分率、电击回避达标各项指标均略优于BF组;双侧海马CA3区局部场电位节律出现去同步化快波改变,右侧海马CA3区出现了θ波和γ 1波百分比的同步性增加,但无θ~γ 1波相位-振幅耦合出现。结论:幼年期短期高脂饮食至青春期的大鼠,尽管体重较基础饲料大鼠增加,但未见Y型迷宫电击回避反应能力和海马依赖性空间认知功能的减退。
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    5-HT1B受体亚型对小脑顶核介导的运动行为的影响
    高伟, 王楠, 乔虎
    中国应用生理学杂志. 2016, 32 (6): 550-554.   DOI: 10.13459/j.cnki.cjap.2016.06.014
    摘要   PDF (918KB)
    目的:探讨5-羟色胺(5-HT)能神经系统在经小脑顶核介导的运动行为中的作用。方法:采用大鼠离体脑片膜片钳及大鼠走步机的行为学测试方法。结果:阻断5-HT1B受体能够增强小脑顶核兴奋性突触传递,行为学试验中给予5-HT及5-HT1B受体阻断剂SB224289,发现注射5-HT到小脑顶核后,大鼠在Rota-rod走步机上的持续时间显著延长,而给予其阻断剂SB224289后,能够反转此作用。结论:5-HT很可能通过5-HT1B受体抑制顶核神经元的兴奋性突触传递从而调节小脑核团神经元环路的活动,继而影响小脑的最终输出,实现对小脑顶核介导的运动平衡和协调能力的调控。
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    阿霉素损伤心肌细胞miRNA378与网腔钙结合蛋白、内质网应激的关系
    赵明, 崔晓雪, 于淼, 王伊林, 龙杰, 赵强
    中国应用生理学杂志. 2016, 32 (6): 555-557.   DOI: 10.13459/j.cnki.cjap.2016.06.015
    摘要   PDF (729KB)
    目的:研究阿霉素损伤心肌细胞miRNA378与网腔钙结合蛋白(calumenin)、内质网应激相关性。方法:原代培养乳鼠心肌细胞分为6组:对照组、阿霉素组、miRNA378过表达对照组、miRNA378过表达组、miRNA378沉默对照组、miRNA378沉默组,采用免疫组化法检测细胞α-SMA蛋白;慢病毒质粒转染心室肌细胞,实时荧光定量PCR技术检测各组心肌细胞miRNA378、calumenin及葡萄糖调节蛋白78(GRP78) mRNA表达。结果:与阿霉素组相比较,miRNA378过表达组心肌细胞calumenin mRNA表达增加(P<0.01),而GRP78 mRNA表达减少(P<0.01);与阿霉素组相比较,miRNA378沉默组calumenin及GRP78 mRNA表达无统计学差异。结论:阿霉素损伤乳鼠心肌细胞是通过减少calumenin蛋白表达进而引起内质网应激,该作用通过上调miRNA378得到缓解。
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    糖尿病并发抑郁症大鼠海马血脑屏障结构的损伤及其机制
    杜青, 王宇红, 赵洪庆, 杨蕙, 孟盼, 徐雅岚
    中国应用生理学杂志. 2016, 32 (6): 558-562.   DOI: 10.13459/j.cnki.cjap.2016.06.016
    摘要   PDF (1067KB)
    目的:研究糖尿病并发抑郁症大鼠海马血脑屏障结构关键蛋白紧密连接蛋白(ZO-1)、基底膜蛋白(CoIV)、周细胞蛋白(a-SMA)的表达情况及其损伤机制。方法:采用高脂灌胃14 d后,再尾静脉注射链脲佐菌素(STZ,38mg/kg),随机分为2组(n=15):糖尿病组和糖尿病并发抑郁症组;正常大鼠随机分为2组(n=15):空白对照组和抑郁症组。糖尿病组与空白对照组正常饲养,糖尿病并发抑郁症组和抑郁症组慢性不可预知性应激28 d。检测各组大鼠血糖值的变化,Open-field及Morris实验评价大鼠行为学变化,透射电子显微镜观察大鼠海马血脑屏障形态学改变,免疫组化法检测大鼠海马血脑屏障关键蛋白ZO-1、CoIV、a-SMA表达情况。结果:与空白对照组比较,糖尿病并发抑郁症组大鼠血糖异常升高,自主活动次数减少,逃避潜伏期延长,空间探索时间减少(P < 0.05,P < 0. 01);海马血脑屏障内皮模糊,毛细血管管腔狭窄,周边胶质细胞终足水肿,ZO-1、α-SMA表达显著减少(P < 0. 05),CoIV的表达显著增加(P < 0.05);与糖尿病组比较,糖尿病并发抑郁症组大鼠自主活动次数显著减少(P < 0. 01),逃避潜伏期延长(P < 0.05),海马血脑屏障毛细血管管腔更为狭窄、胶质细胞终足水肿更为明显,a-SMA表达显著下降(P< 0.05)。结论:糖尿病并发抑郁症血脑屏障关键蛋白ZO-1、CoIV、α-SMA表达紊乱可能是其结构损伤发生机制之一。
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    当归黄芪提取物对慢性腹膜功能衰竭大鼠腹膜功能、结构及TGF-β1表达的影响
    杜丽东, 吴国泰, 王凤玲, 张瑛, 任远
    中国应用生理学杂志. 2016, 32 (6): 563-566.   DOI: 10.13459/j.cnki.cjap.2016.06.017
    摘要   PDF (663KB)
    目的:观察当归黄芪提取物(EAA)对大鼠腹膜功能、结构及转化生长因子β1(TGF-β1)表达的影响。方法:50只SD大鼠随机分为正常对照组、模型对照组、阳性对照组、EAA高、低剂量组(n=10)。除正常对照组外,其余4组大鼠每天腹腔注射4.25%高糖腹透液100 ml/kg,连续40 d,并在第8天、10天、12天腹腔注射大肠杆菌脂多糖(LPS)5 mg/kg,建立大鼠慢性腹膜功能衰竭模型,造模的同时灌胃给予相应药物。通过称大鼠体重和观察活动状态,测定超滤量、腹膜转运功能参数、壁层腹膜厚度、壁层腹膜TGF-β1的表达,研究EAA对大鼠腹膜功能、结构的保护作用及TGF-β1表达的影响。结果:EAA能升高高糖腹膜透析液联合LPS诱发的腹膜功能衰竭大鼠超滤量和腹膜转运功能参数;使大鼠腹膜增厚程度降低,TGF-β1表达减少。结论:EAA对大鼠腹膜功能、结构具有一定的保护作用且能抑制TGF-β1表达。
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    双受体激动剂CI-1206拮抗Aβ1-42所致小鼠空间学习记忆损伤的作用
    杨菊, 张军, 原丽, 曲雪松, 祁金顺
    中国应用生理学杂志. 2016, 32 (6): 567-570.   DOI: 10.13459/j.cnki.cjap.2016.06.018
    摘要   PDF (1098KB)
    目的:探讨葡萄糖依赖性促胰岛素释放激素(GIP)和胰高血糖素样肽1(GLP-1)双受体激动剂CI-1206拮抗淀粉样β蛋白(Aβ)所致小鼠空间工作记忆及长时程记忆损伤的作用。方法:C57小鼠经侧脑室注射Aβ1-42寡聚体建立AD动物模型,经腹腔注射CI-1206进行药物干预,随机分为对照组(saline + D-PBS)、Aβ1-42 + saline、CI-1206+ D-PBS、Aβ1-42 + CI-1206组(n=12),而后联合应用Y-迷宫和Morris水迷宫行为学手段检测小鼠空间学习记忆。结果:①Aβ1-42 + saline组小鼠在Y迷宫自发交替实验中进臂正确百分比明显低于对照组(P < 0. 05);Aβ1-42 + CI-1206组则明显高于单独给予Aβ1-42组(P < 0.05);②Morris水迷宫结果显示,与对照组相比,Aβ1-42 + saline组的小鼠逃避潜伏期明显延长,目标象限游泳时间百分比降低(P < 0. 05),经CI-1206处理可明显改善(P < 0. 05);③Aβ1-42和CI-1206均不影响小鼠的运动能力和视力。结论:脑室注射Aβ影响小鼠短期工作记忆及长期空间学习记忆能力;腹腔注射CI-1206可拮抗Aβ1-42所致的短期和长期记忆损伤。
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    TLR4/P38/JNK信号通路在海马神经元凋亡中的作用
    蒋伟, 张弦, 周爱玲
    中国应用生理学杂志. 2016, 32 (6): 571-576.   DOI: 10.13459/j.cnki.cjap.2016.06.019
    摘要   PDF (1355KB)
    目的:探讨Toll样受体4(TLR4)/P38/JNK信号通路在海马神经元凋亡中的作用及其机制,为神经退行性疾病(ND)的发病机制与防治研究提供新的实验依据。方法:采用体外培养7 d的新生大鼠海马神经元,免疫荧光双标法鉴定海马神经元纯度。用TLR4配体脂多糖(LPS)或TLR4抗体预处理海马神经元,以激活或阻断TLR4的作用。实验1设正常对照组、LPS组及TLR4抗体+ LPS组;免疫荧光法检测P-P38,P-JNK的表达。实验2分为6组:正常对照组,LPS组,TLR4抗体+ LPS组,SB202190(抑制P38) + LPS组,SP600125(抑制JNK) + LPS组,PD98059(抑制ERK) + LPS组;分别用TLR4抗体、P38、JNK及ERK的抑制剂预处理海马神经元后再给以LPS刺激24 h,Western blot法检测Bcl-2,Bax,Active-caspase-3的表达变化;流式细胞术检测海马神经元凋亡率。结果:LPS组海马神经元P-P38、P-JNK的表达明显高于正常对照组(P < 0. 01),TLR4抗体+ LPS组P-P38,P-JNK表达显著低于LPS组(P <0.01)。与正常对照组相比,LPS组海马神经元Bcl-2/Bax表达减少、Active-caspase-3表达增加,海马神经元凋亡率增加(P < 0.01)。而TLR4抗体+ LPS组、SB202190 + LPS组、SP600125 + LPS组Bcl-2/Bax显著高于LPS组、Active cas-pase-3显著低于LPS组(P < 0.01),海马神经元凋亡率显著低于LPS组(P < 0. 05,P < 0. 01)。PD98059 + LPS组与LPS组海马神经元凋亡率无明显差异。结论:①海马神经元中有TLR4介导的P38/JNK信号通路。②海马神经元TLR4激活后,P-P38、P-JNK表达增加,使Bcl-2/Bax的比例降低和Active-caspase-3表达增加,从而促进海马神经元的凋亡。海马神经元凋亡过程中有TLR4介导的P38/JNK信号通路的参与。
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