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复方GC提取物抗心律失常的药效学及机理研究
【作者】 万军；
【导师】 黄国钧；
【作者基本信息】 成都中医药大学 ， 中药学， 2008， 博士
【摘要】 目的:心律失常是多种心脏病严重的症状表现及致死的主要原因之一。通过探讨复方GC提取物的抗心律失常作用,并探索其作用机理,为复方GC提取物创新药物的研究提供药理学依据。方法:实验采用药物诱发心律失常动物模型研究复方GC提取物抗心律失常作用。观察复方GC提取物对氯仿诱发小鼠室颤的预防作用,采用乌头碱诱发小鼠、大鼠心律失常模型;氯化钙、氯化钡、垂体后叶素诱发大鼠心律失常模型;毒毛花苷K诱发豚鼠心律失常模型,记录出现心律失常的潜伏时间及持续时间。采用拮抗肾上腺素及乙酰胆碱诱发大鼠心律失常的作用,阐明其通过调整心脏交感神经和迷走神经功能而缓解心律失常的作用机理。采用邻苯三酚法测定垂体后叶素诱发心律失常小鼠心脏超氧化物歧化酶(SOD)活性及硫代巴比妥酸(TBA)法测定过氧化脂质(LPO)含量,以揭示复方GC提取物抗心肌氧化损伤的机理;采用一氧化氮合酶(NOS)及一氧化氮(NO)试剂盒测定垂体后叶素诱发心律失常小鼠心脏及血清NOS活性及NO含量以揭示复方GC提取物扩张血管,改善心肌血流量的作用机理。所有实验数据均SPSS 13.0 for Windows统计分析软件分析处理,数据用(?)±s表示。结果:复方GC提取物对氯仿诱发小鼠室颤,乌头碱诱发小鼠心律失常,乌头碱、肾上腺素、垂体后叶素诱发大鼠心律失常及毒毛花苷K诱发豚鼠心律失常均有较好的预防作用,药效呈浓度依赖性;对乙酰胆碱诱发大鼠心动过缓有一定拮抗作用;对氯化钙、氯化钡诱发的大鼠心律失常效果较差。作用机理研究表明复方GC提取物能通过调整心脏交感神经和迷走神经功能而缓解心律失常,并升高心律失常小鼠心脏及血清SOD及NOS活性,降低LPO含量及增加NO含量。结论:复方GC提取物具有抗实验性心律失常作用,且有一定的量效关系。其机理可能与调整心脏交感神经和迷走神经功能、抗心肌氧自由基损伤,扩张心肌组织血管,增加心肌血流量及改善循环有关。
【Abstract】 Objective: Cardiac arrhythmia is serious symptom in the heart diseases and one of the main dead reasons.In order to study GC compound, we did research on the antiarrhythmic action and the mechanism.Methods: To investigate the protective effects of GC compound on experimental arrhythmia, arrhythmic animal models were established by different drugs. The preventive effects of ventricular fibrillation produced by chloroform inhalation in mice were observed. Through the arrhythmic rats&mice models established by aconitine, the antiarrhythmic effects of GC compound were evaluated. Making the arrhythmia rat models with alcium chloride, barium chloride and pituitrin respectively.The effects on arrhythmic model of Guinea pig produced by strophantin K were studied. The evaluating indicators were latent time & duration of cardiac arrhythmia. We investigated the effects of GC compound on arrhythmic rats established by adrenaline and acetylcholine (Ach) respectively to clarify the mechanism through adjusting the function of heart sympathetic nerve & pneumogastric nerve. Lipid peroxidation (LPO) content was measured with thiobarbituric acid chromatometry and the method of pyrograllol autoxidation was used to determine superoxide dismutase (SOD) .We examined the content of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in serum and cardiac muscle. Through these researches, the function of GC compound on the anoxemia of cardiac muscle and free radical were investigated. All data were processed by SPSS13. 0 for Windows and presentation of experiment results in (x|-)±s.Results: The effects of GC compound on five different experimental models of arrhythmia are obvious and concentration dependent, except calcium chloride and barium chloride.It can increase the activities of SOD and NOS, improve the NO concentration and decrease LPO level.Conclusion : It has been discovered in experimental researches that GC compound has antiarrhythmia effects which displays certain dosage-effect relationship. Its mechanism may be associated with adjusting the function of heart sympathetic nerve & pneumogastric nerve, eliminating free radical, dilating blood vessel and improving microcirculation.