桂枝甘草龙骨牡蛎加味汤对大鼠冠心病室性早搏及血清NO、ET-1水平的影响

Modified Guizhi Gancao Longgu Muli Decoction Has Effect on Ventricular Premature Beats and Levels of NO and ET-1 in Serum in Rats with Coronary Heart Disease

目的:探讨桂枝甘草龙骨牡蛎加味汤对大鼠冠心病室性早搏(VP)及血清一氧化氮(NO)、内皮素-1 (ET-1)水平的影响。方法:将30只大鼠随机分为中药组、中成药组、西药组、模型组、空白组,每组6只。除空白组外,用高脂饲料喂养及注射垂体后叶素制备冠心病VP模型。模型制备成功后,中药组按6.3 g/kg的剂量灌胃桂枝甘草龙骨牡蛎加味汤,中成药组按85 mg/kg的剂量灌胃复方丹参滴丸,西药组按2.1 mg/kg的剂量灌胃辛伐他丁,模型组及空白组按20 mL/kg的剂量灌胃生理盐水。每天1次,连续12周。记录模型制备前及末次给药后24 h动态心电图。观察各组大鼠心电图ST段、血脂水平、早搏情况,用硝酸还原酶法测定NO水平,用酶联免疫吸附法测定ET-1水平。结果:末次给药后24 h后,与空白组比较,模型组ST段及低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、总胆固醇(TC)、ET-1水平均升高(P<0.05),VP潜伏期缩短(P<0.05),血清NO水平升高(P<0.05),VP持续时间延长(P<0.05)。与模型组比较,中药组、中成药组及西药组的ST段及LDL-C、TG、TC、ET-1水平均下降(P<0.05),VP潜伏期延长(P<0.05),HDL-C及血清NO水平升高(P<0.05),VP持续时间均缩短(P<0.05);与中药组比较,中成药组及西药组ST段及LDL-C、TG、TC、HDL-C、ET-1水平升高,VP潜伏期延长(P<0.05),血清NO水平降低(P<0.05)。结论:桂枝甘草龙骨牡蛎加味汤可促进大鼠冠心病VP心肌供血,调节血脂水平,且可明显提高血清NO水平,降低ET-1水平,对冠心病VP有较好的预防作用。

Objective:To discuss the effect of modified Guizhi Gancao Longgu Muli decoction on ventricular premature(VP) beats and levels of nitric oxide(NO) and endothelin-1(ET-1) in serum in rats with coronary heart disease. Methods:A total of 30 rats were randomly divided into the Chinese medicine group,the Chinese patent medicine group,the western medicine group,the model group,and the blank group,six rats in each group. Except for the blank group,the other groups were fed with high-fat diet and injected with pituitrin to establish the model of VP in coronary heart disease. After successful establishment,the Chinese medicine group was given gastric perfusion of modified Guizhi Gancao Longgu Muli decoction at a dose of 6.3 g/kg;the Chinese patent medicine group was given gastric perfusion of compound Danshen dripping pills at a dose of 85 mg/kg;the western medicine group was given simvastatin at a dose of 2.1 mg/kg by gavage;the model group and the blank group were given normal saline at a dose of 20 mL/kg by gavage. All groups were given gastric perfusion once a day for 12 weeks. The 24-hour dynamic electrocardiogram was recorded before establishment and after the last gastric perfusion. The ST segment of electrocardiogram,the level of blood lipid,and the condition of premature beats in each group were observed. The level of NO was measured by nitrate reductase method,and the level of ET-1 was detected by enzymelinked immunosorbent assay. Results:When compared with those in the blank group 24 hours after the last administration,in the model group,the ST segment,the levels of low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C),triglyceride(TG),total cholesterol(TC),and ET-1 were increased(P<0.05);and the latency of VP was shortened(P<0.05);the level of NO in serum was decreased(P<0.05), and the duration of VP was prolonged. Compared with those in the model group, in the Chinese medicine group, the Chinese patent medicine group, and the western medicine group,the ST segment,the levels of LDL-C,TG,TC and ET-1 were decreased(P<0.05);and the latency of VP was prolonged(P<0.05);the levels of HDL-C and NO in serum were increased(P<0.05);the duration of VP was shortened(P<0.05). Compared with those in the Chinese medicine group, in the Chinese patent medicine group and the western medicine group,the ST segment,the levels of LDL-C,TG,TC,HDL-C and ET-1 were increased,and the latency of VP was prolonged(P<0.05);the levels of NO in serum were decreased(P<0.05). Conclusion:Modified Guizhi Gancao Longgu Muli decoction can promote myocardial blood supply and regulate the level of blood lipid in rats with coronary heart disease and VP. Besides, it can significantly enhance the level of NO in serum, and reduce the level of ET-1, which has good preventive effect on VP in coronary heart disease.