益气活血方对心肌梗死大鼠心肌细胞坏死与凋亡的影响

目的通过观察益气活血方对心肌梗死大鼠心肌细胞坏死与凋亡的影响来探讨益气活血方对心肌梗死大鼠心肌的保护作用及可能机制。方法将雄性SD大鼠随机分为假手术组、模型组、益气活血组、培哚普利组。结扎冠状动脉左前降支复制心肌梗死动物模型,造模成功后,益气活血方组予益气活血方(合生药量21 g/kg)每日1次灌胃,培哚普利组予培哚普利(0.4 mg/kg)每日1次灌胃,假手术组、模型组不进行药物干预,予以无菌蒸馏水灌胃。于治疗后7、28 d 2个时间点腹主动脉取血,并取心脏梗死边缘区组织进行相关指标检测。运用超声心动检测大鼠心脏形态学和功能学变化:左室射血分数(LVEF)、左室短轴率(LVFS)、左室收缩末期内径(LVIDs)、左室舒张末期内径(LVIDd);以ELISA方法检测血清超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px),肌酸激酶(CK),乳酸脱氢酶(LDH),谷草转氨酶(AST),肌钙蛋白(c Tn T)的变化。运用蛋白质印迹法(Western Blot)观察心肌组织梗死边缘区细胞色素C(cyt C),半胱氨酸天冬氨酸蛋白酶-3(caspase-3)蛋白表达情况。结果 7 d时,与模型组比较,益气活血组和培哚普利组LVEF、LVFS明显升高(P0.05),LVIDs、LVIDd呈缩减趋势,但无统计学差异(P0.05)。28 d时,与模型组比较,益气活血组和培哚普利组LVEF、LVFS明显升高(P0.05)。益气活血组LVIDs、LVIDd明显降低(P0.05),培哚普利组LVIDd明显降低(P0.05),LVIDs降低,但无统计学差异(P0.05)。与模型组比较,益气活血组和培哚普利组7 d和28 d时CK-MB、LDH、AST、c Tn T明显降低,SOD、GSH-PX明显升高,均有统计学差异(P0.05);7 d时益气活血组和培哚普利组cyt C、caspase-3蛋白表达明显降低,有统计学差异(P0.05)。结论早期运用益气活血方可有效改善心肌梗死大鼠心脏结构与功能变化,提高大鼠心肌细胞抗氧化能力,抑制心肌细胞凋亡与坏死。

Effects of Yiqi Huoxue Fang on necrosis and apoptosis of myocardial cell in rats with myocardial infarction

Objective To explore the protective effects of Yiqi Huoxue Fang(Qi-boosting Blood-activa-ting Formula,YQHXF)on rat myocardium with myocardial infarction and its possible mechanism by ob-serving the effects of YQHXF on necrosis and apoptosis of myocardial cell necrosis.Methods Male SD rats were randomly divided into the sham-surgery group,model group,YQHXF group,and perindopril group.Animal model of myocardial infarction was built by ligating coronary artery on the left anterior de-scending branch.Subsequently,YQHXF group received intragastric administration of Yiqi Huoxue Fang (compound medicine,21 g/kg)once per day,and perindopril group was given perindopril (0.4 mg/kg)once a day;Sham-surgery group and model group received sterile distilled water without drug inter-vention.The blood in abdominal aorta was drawn,and the tissue on the peripheral area of the myocardial infarction was taken at two fixed time points (on the 7 th and 28 th day)after administration.Ultrasonic ech-ocardiography was used to detect changes on cardiac morphology and function in rats:left ventricular e-jection fraction (LVEF),left ventricular short axis ratio (LVFS),left ventricular end systolic diameter (LVIDs),left ventricular end-diastolic diameter (LVIDd);serum superoxide dismutase (SOD),gluta-thione peroxidase (gsh-px),creatine kinase (CK),lactate dehydrogenase (LDH),aspertate amin-otransferase (AST),and troponin (cTnT)were measured with ELISA method.Protein imprinting meth-od (Western Blot)was used to measure cytochrome C (CytC)and protein expression of cysteine aspartic acid and protease-3 (caspase-3)in the border zone of infarcted area.Results On the 7 th day,com-pared with the model group,LVEF and LVFS in YQHXF group and perindopril group decreased without statistical significance(P >0.05).On the 28 th day,compared with the model group,LVEF and LVFS in YQHXF group and perindopril group increased significantly(P >0.05 ).LVIDs and LVIDd decreased markedly(P <0.05);LVIDd in perindopril group decreased sharply (P <0.05),and decrease presen-ted on LVIDs without statistical significace (P >0.05).On the 7 th and 28 th day,compared with the mod-el group,CK-MB,LDH,AST,cTnT in YQHXF group and perindopril group decreased significantly (P<0.05),and SOD,GSH-PX increased significantly.On the 7 th day,protein expression of cytC,caspase-3 decreased significantly in YQHXF group and perindopril group(P <0.05).Conclusion Administra-tion of YQHXF at early stage can effectively improve myocardial infarction on cardiac structure and func-tion in rats with myocardial infarction,improve oxidation resistance of myocardial cell,and inhibit myo-cardial apoptosis and necrosis.