交趾黄檀提取物对大鼠急性心肌缺血的保护作用及机制研究  

Protective Effect and Mechanism of Dalbergia cochinchinensis Extract on Acute Myocardial Ischemia in Rats

作　　者：欧阳灿玥 李安 陈兰英[1,2] 汪文龙 张莹 徐维欣 罗颖颖[1,2] 刘荣华 OUYANG Canyue;LI An;CHEN Lanying;WANG Wenlong;ZHANG Ying;XU Weixin;LUO Yingying;LIU Ronghua(National Pharmaceutical Engieering Center for Solid Preparation in Chinese Herbal Medicine,Nanchang 330006,China;College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]中药固体制剂制造技术国家工程研究中心,南昌330006 [2]江西中医药大学药学院,南昌330004

出　　处：《中国药学杂志》2023年第17期1563-1572,共10页Chinese Pharmaceutical Journal

基　　金：国家重点研发计划资助(2018YFC1706102);国家自然科学基金项目资助(82160732)。

摘　　要：目的探讨交趾黄檀提取物对大鼠冠状动脉左前降支结扎所致急性心肌缺血的心脏保护作用及可能机制。方法60只SD雄鼠随机分为假手术组、模型组、尼可地尔(3 mg·kg^(-1))组、交趾黄檀提取物组(1.5、3和6 g·kg^(-1)),每组10只,通过结扎冠脉左前降支建立大鼠急性心肌缺血模型,造模24 h后给药,连续10 d每天给药1次,假手术组和模型组给予相应剂量的蒸馏水,末次给药1h后进行观察和取材。PowerLab电生理记录仪检测大鼠血流动力学指标动脉收缩压(systolic blood pressure,SBP)、动脉舒张压(diastolic blood pressure,DBP)、平均血压(mean blood pressure,MBP)、左室收缩压(left ventricular systolic pressure,LVSP)、等容收缩期左心室内压最大上升和下降速率(±maximal left ventricular pressure rising rate,±dp/dtmax);HE染色观察心肌病理变化;生化法检测血清中乳酸脱氢酶(lactic dehydrogenase,LDH)、肌酸激酶同工酶(creatine kinase-MB,CKMB);定磷法测定心肌组织中Ca2+-ATP酶活力;检测血浆中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、葡萄糖(glucose,GLU)、乳酸(lactate,LA)的含量;RT-PCR法检测心肌组织中腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)、过氧化物酶体增殖物激活受体γ辅激活因子-1α(peroxisome proliferator activated receptorγcoactivator 1α,PGC-1α)、脂肪酸转位酶(fatty acid translocase gene,CD36)、长链酰基辅酶a合成酶1(long-chain acyl-CoA synthetase 1,ACSL1)、丙酮酸激酶(pyruvate kinase M,PKM)、磷酸果糖激酶2(phosphofructokinase 2,PFK2)mRNA的表达。Western Blot法检测心肌组织磷酸化AMPK(p-AMPK)、AMPK、PGC-1α蛋白表达水平。结果与模型组相比,交趾黄檀提取物中、高剂量组可显著升高大鼠SBP,各给药组均可升高心肌缺血大鼠DBP和MBP,LVSP和±OBJECTIVE To investigate the protective effect and possible mechanism of Dalbergia cochinchinensis extract on acute myocardial ischemia induced by left anterior descending coronary artery ligation in rats.METHODS A rat model of acute myocardial ischemia was established by ligation of the left anterior descending coronary artery.Sixty SD male rats were randomly divided into sham operation group,model group(MI),nicorandil(3 mg·kg^(-1))group,and Dalbergia cochinchinensis extract groups(1.5,3 and 6 mg·kg^(-1)).After 24 hours of modeling,the rats in the latter two groups were administered with drug once a day for 10 days,and the corresponding volume of distilled water was given to the sham operation group and model group.After 1 hour of the last administration,the rats were observed and sacrificed.The hemodynamic parameters of systolic blood pressure(SBP),diastolic blood pressure(DBP),mean blood pressure(MBP),left ventricular systolic pressure(LVSP),and the maximum rate of increase/decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)were detected by PowerLab electrophysiological recorder.HE staining was used to observe the pathological changes of infarction area;lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CKMB)in serum were detected by biochemical method.Glucose,lactate,Ca2+-ATPase,and blood lipid in plasma were detected.The expressiosn of AMPK,PGC-1α,CD36,ACSL1 and PFK2 mRNA in myocardial tissue were detected by RT-PCR.The protein expression levels of phosphorylated AMPK(p-AMPK),AMPK and PGC-1αin myocardial tissue were detected by Western Blot.RESULTS Compared with the model group,Dalbergia cochinchinensis extracts could significantly increase the R value of rat soles and the B value of auricles and improve the darkness.SBP,DBP,MBP,LVSP and±dp/dtmax were significantly increased in Dalbergia cochinchinensis extract groups.HE staining showed that Dalbergia cochinchinensis extract of all dosages could significantly improve the pathological damage of myocardial infarction area

关 键 词：交趾黄檀 心肌缺血 心肌损伤 能量代谢 

分 类 号：R966[医药卫生—药理学]