枳桂舒心颗粒对模型缺血心肌保护作用机制研究

摘要

目的：观察枳桂舒心颗粒对痰浊（食饵性高血脂）合并缺血性心肌损伤模型大鼠的影响，探讨枳桂舒心颗粒对实验性缺血心肌的保护作用机制。方法选取心电图正常的Wistar大鼠60只，随机分为6组，即空白组、模型组、阳性对照组、枳桂舒心颗粒高剂量组、枳桂舒心颗粒中剂量组、枳桂舒心颗粒低剂量组，每组10只。观察记录动物标准Ⅱ导联心电图，计算大鼠在腹腔注射异丙肾上腺素后心电图ST段偏移毫伏数，观察心肌缺血程度。检测心肌三酶（ LDH、CK、AST）、血脂（ TG、CHO、HDL-C、LDL-C）、血小板活化因子（ TXB2、6-k-PGF1α）、MDA、SOD等指标，观察枳桂舒心颗粒对缺血性心肌损伤影响。结果枳桂舒心颗粒可减轻异丙肾上腺素所致大鼠缺血性心肌损伤模型心肌损伤程度。枳桂舒心颗粒高、中、低剂量组和阳性对照组大鼠血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）、天冬氨酸氨基转移酶（AST）的含量均低于模型组（P﹤0.05，P﹤0.01），枳桂舒心颗粒高、中、低剂量组和阳性对照组TG、CHO、LDL-C3项指标均低于模型组（ P﹤0.05，P﹤0.01）；枳桂舒心颗粒高、中、低剂量组和阳性对照组HDL-C的检测指标均高于模型组（ P﹤0.05，P﹤0.01）。枳桂舒心颗粒高、中、低剂量组和阳性对照组血清中TXB2、MDA含量均低于模型组，（ P﹤0.05，P﹤0.01）；枳桂舒心颗粒高、中、低剂量组和阳性对照组血清中6-k-PGF1α、SOD含量均高于模型组（ P﹤0.05，P﹤0.01）。结论通过实验研究表明，枳桂舒心颗粒对心肌缺血所致心肌损伤有减轻作用，其作用机制可能与枳桂舒心颗粒能减轻心肌细胞损伤、改善痰浊（食饵高血脂）模型大鼠脂类代谢，延缓动脉粥样硬化的发展，降低心肌耗氧量，抑制血小板聚集，抗自由基损伤等对心肌损伤起到一定保护作用。%Objective To observe the effect of Zhigui Shuxin Granules on phlegm-turbid( diet-induced hyperlipi-demia)combined with ischemic myocardial injury model rats,to explore the protection mechanism of Zhigui Shuxin Granules on experimental myocardial ischemia. Methods Select 60 Wistar rats with normal standardⅡlead electrocar-diogram( ecg),divide them into 6 groups:blank group,model group,positive control group,high dose of Zhigui Shuxin Granules group,medium dose of Zhigui Shuxin Granules group,and low dose of Zhigui Shuxin Granules group,with 10 rats in each group. Use high fat diet and intraperitoneal injection of isopropyl adrenaline to copy phlegm-turbid combined with ischemic myocardial injury model rats. Observe and record animal standardⅡlead electrocardiogram(ecg),calcu-late the ecg ST segment number millivolt of rats after intraperitoneal injection of isopropyl adrenaline and observe the de-gree of myocardial ischemia. After electrocardiogram( ecg)test,take the blood of rats in the condition of anesthesia by abdominal aorta puncture,heparin anticoagulation,detect myocardial three enzymes( LDH,CK,AST),blood lipid( TG, CHO,HDL and LDL)and platelet activating factor( TXB2,6-k-PGF1α),MDA,SOD and other indicators,observe the effect of Zhigui Shuxin Granules on ischemic myocardial injury. Results The calculation of myocardial ischemia degree results showed that Zhigui Shuxin Granules could reduce the degree of myocardial damage in ischemic myocardial injury model rats caused by isopropyl adrenaline. The myocardial three enzyme test results showed that serum creatine kinase (CK),lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)activity of rats in high,medium and low dose of Zhigui Shuxin Granules groups and positive control group were lower than those of the model group,the differ-ence had statistically significance(P﹤0. 05,P﹤0. 01). The three acyl glycerin(TG),total cholesterol(CHO),low-density lipoprotein( LDL),high-density lipoprotein( HDL)test showed that TG,CHO,LDL3 indicators in the high,me-dium and low dose of Zhigui Shuxin Granules groups and positive control group were lower than those of the model group,the difference had statistically significance(P﹤0. 05,P﹤0. 01);The HDL test index of the high,medium and low dose of Zhigui Shuxin Granules groups and positive control group were higher than that of the model group,the difference had statistically significance(P﹤0. 05,P﹤0. 01). The platelet activating factor(TXB2,6-k-PGF1α),MDA, SOD test results showed that serum TXB2,MDA content of the high,medium and low dose of Zhigui Shuxin Granules groups and positive control group were lower than those of the model group,the difference had statistically significance ( P﹤0. 05,P﹤0. 01);The serum 6-k-PGF1α,SOD content of the high,medium and low dose of Zhigui Shuxin Granules groups and positive control group were higher than those of the model group,the difference had statistically significance (P﹤0. 05,P﹤0. 01). Conclusion The experimental research indicated that Zhigui Shuxin Granules could alleviate myocardial injury caused by myocardial ischemia and its mechanism might be related to Zhigui Shuxin Granules’reduc-ing myocardial cell injury,improving the lipid metabolism of the phlegm turbidity( diet-induced hyperlipidemia)model rats,delaying the development of atherosclerosis,reducing myocardial oxygen consumption,inhibiting of platelet aggrega-tion,fighting against free radical damage on myocardial injury and etc,and it played a certain protective effect on myo-cardial injury. This had provided reliable theory basis for the Zhigui Shuxin Granules’application in the treatment of coronary heart disease and angina,while its effect mechanism still needed further research.