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作 者:安薇[1] 杨静[1] 张建忠 汪俊军 刘茂南[2]
机构地区:[1]武汉大学医学院药理学系 [2]武汉市新洲区人民医院
出 处:《中国临床药理学与治疗学》2005年第7期776-780,共5页Chinese Journal of Clinical Pharmacology and Therapeutics
基 金:湖北省武汉市科技局科学技术计划项目(№Z20036002009)
摘 要:目的:研究平律复方(PL)抗实验性心律失常的作用,并初步探讨其作用机理。方法:采用氯仿、氯化钙以及心肌缺血再灌注三种心律失常动物模型,监测标准Ⅱ导联心电图;测定缺血再灌注大鼠血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;放射配基受体结合法分析心肌组织血小板激活因子(plate-let activating factor,PAF)受体蛋白表达水平;RT-PCR法检测PAF受体mRNA表达水平;测定心肌脂质过氧化产物丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:PL(ig,0.04、0.20、1.00 g.kg-1)对氯仿引起的小鼠心室纤颤有一定的保护作用;能减少氯化钙致大鼠室颤的发生率,降低死亡率;可显著降低心肌缺血再灌注大鼠心律失常的发生率,缩短持续时间,与模型对照组比较,PL小、中、大剂量组心肌CK和LDH分别降低了35.4%、51.8%、57.5%和22.4%、34.4%、38.4%;剂量依赖性下调心肌细胞PAF受体蛋白及mRNA表达水平,升高心肌SOD活性、降低MDA含量。结论:PL对氯仿、氯化钙以及心肌缺血再灌注诱发的心律失常均有较好的保护作用,其作用机制可能与下调心肌细胞PAF受体水平,抑制脂质过氧化有关。AIM:To investigate the protective effects of PL compound on experimental arrhythmias. METHODS: 3 arrhythmic animal models which inhalation of chloroform to induce ventricular fibrillation (VF) in mice, CaCl2 to induce arrhythmia and myocardial to induce ischemia-reperfusion in rats. At the same time, the changes were observed by lead Ⅱ dynamic ECG. The activities of LDH, CK were determined, respectively. PAF receptor level in myocardial cell of rats was studied by HPAF radio legend binding and RT-PCR. Contents of SOD and MDA of myocardium were assayed, respectively. RESULTS: PL (0.04, 0.20, 1.00 g·kg^-1, ig) was shown to protect mice which suffering from VF induced by chloroform, decrease the incidence of VF and death induced by CaCl2 in rats and shorten duration of ventricular arrhythmia and eliminate the incidence of VF in rats induced by myocardial ischemia-reperfusion. The activities of LDH, CK were reduced by 35.4%, 51.8%, 57.5% and 22.4%, 34.4%, 38.4% when compared with model group. PL compound inhibited PAF receptor level of myocardial cells in dose-dependent manner, increased the activities of SOD and decreased the contents of MDA. CONCLUTION: PL compound has obvious antiarrhythmic effects, the protective action is related to decreasing the expression of PAF receptor of myocardial cells and anti-lipid peroxydation reaction.
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