芍药苷通过cAMP-PKA信号通路对心肌梗死大鼠保护作用的实验研究  

Study on the protective effect of paeoniflorin against myocardial infarction in rats by the cAMP-PKA singal pathway

作　　者：王建发[1] 赵国安[2] Wang Jianfa;Zhao Guoan(Department of cardiology,the third affiliated Hospital of Xinxiang medical College,Henan 453003,China)

机构地区：[1]河南省新乡医学院第三附属医院心血管内二科,新乡453003 [2]河南省新乡医学院,新乡453003

出　　处：《中国循证心血管医学杂志》2018年第4期479-483,共5页Chinese Journal of Evidence-Based Cardiovascular Medicine

摘　　要：目的探讨芍药苷对心肌梗死大鼠的保护作用,并初步探究其分子机制。方法选取50只大鼠结扎冠状动脉制作心梗模型,将造模成功大鼠分为模型组(等量生理盐水)、阳性对照组(10 mg/kg缬沙坦)、芍药苷高(100 mg/kg)、中(50 mg/kg)、低(25 mg/kg)剂量组,每组10只;另选10只作为假手术组,不结扎,其余操作同造模组,假手术组给予等量生理盐水。灌胃给药4周,观察各组大鼠心电图ST段变化、血清酶学变化、心肌组织病理情况、心肌梗死面积,并测定心肌组织中c AMP、PKA及p PKA的表达变化。结果造模组心电图中导联S-T段明显抬高,提示心肌梗死模型造模成功,可供后续实验;给药4周后,各治疗组大鼠血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)活性均显著降低(P<0.05),超氧化物歧化酶(SOD)活性均显著升高(P<0.05),且芍药苷高剂量组血清激酶指标接近假手术组;各治疗组均能明显改善心肌细胞核固缩、碎裂、坏死等;各治疗组大鼠心肌梗死面积均显著减小(P<0.05);各治疗组大鼠心肌组织中c AMP、p PKA、p CREB的表达水平均显著上调(P<0.05)。结论芍药苷可能通过c AMP-PKA信号通路发挥对心肌梗死大鼠的保护作用,且治疗作用呈剂量相关性,可为临床芍药苷治疗心肌梗死提供理论参考。Objective To investigate the protective effect of paeoniflorin against myocardial infarction（MI） in rats and explore preliminaryly the related molecular mechanism involved. Methods 50 rats were selected to establish MI model by ligating coronary artery and randomly divided into the model group（constant volume normal saline）, positive control group（10 mg/kg vassartan）, high paeoniflorin dose group（100 mg/kg,）, medium paeoniflorin dose group（50 mg/kg） and low paeoniflorin dose group（25 mg/kg）, with 10 rats in each group. Another 10 rats were selected as sham-operation group（constant volume normal saline）, which experienced the same procedure with MI model without ligation. All the rats were given continuously for 4 weeks. The changes of S-T segment, serogical examination, myocardial histopathology and myocardial infarct size were observed, and the expression levels of c AMP, PKA in myocardial tissue were determined. Results The S-T segment in electrocardiogram of operated rats was significantly elevated, suggesting that the model of MI was successful, which could be used for subsequent experiments. Four weeks after the treatment, the treatment group rats serum CK, LDH activity were significantly lower（P0.05）. SOD activity was significantly increased（P0.05）, and paeoniflorin high dose group was close to control group in serogical examination. The treatment group can significantly improve the myocardial nucleus fixation, fragmentation, necrosis and so on. The area of myocardial infarction of rats in each treatment group significantly decreased（P0.05）. The expression levels of c AMP and p PKA, p CREB in the myocardial tissue of treated rats were significantly increased（P0.05）. Conclusion Paeoniflorin may play a protective role in myocardial infarction by the c AMP-PKA signal pathway and the therapeutic effect is dose-dependent, which can provide a theoretical reference for the clinical treatment of myocardial infarction.

关 键 词：芍药苷 心肌梗死 环磷酸腺苷 环磷酸腺苷依赖的蛋白激酶 磷酸化蛋白激酶 信号通路 

分 类 号：R542.22[医药卫生—心血管疾病]