目的 探究荆防颗粒对异丙肾上腺素（isoproterenol，ISO）诱导大鼠急性心肌梗死的保护作用。方法 SD大鼠随机分为对照组、模型组、普萘洛尔（10 mg/kg）组和荆防颗粒高、低剂量（32、16 g/kg）组，每组8只。各给药组大鼠ig相应药物，1次/d，连续14 d；第13天给药2 h后，除对照组外，其余组大鼠皮下多点注射ISO （85 mg/kg），对照组sc等体积的生理盐水，连续2 d。心电图观察大鼠ST段的变化；超声心动检查大鼠左心室射血分数（ejection fraction，EF）和短轴缩短率（fractional shortening，FS）；取心脏，计算心脏指数（heart weight index，HWI）；采用苏木素-伊红（HE）染色观察心肌组织病理变化；采用2，3，5-氯化三苯基四氮唑（triphenyltetrazolium chlorinated，TTC）法检测心肌梗死面积；采用全自动生化分析仪检测血清中乳酸脱氢酶（lactate dehydrogenase，LDH）、肌酸激酶同工酶（creatine kinase isoenzyme，CK-MB）、天冬氨酸氨基转移酶（aspartate transaminase，AST）活性及总胆固醇（total cholesterol，TC）、三酰甘油（triglycerides，TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）和高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平；采用试剂盒检测大鼠心肌组织中超氧化歧物酶（superoxide dismutase，SOD）、过氧化氢酶（catalase，CAT）、Na⁺，K⁺-ATP酶、Ca²⁺，Mg²⁺-ATP酶活性及丙二醛（malondialdehyde，MDA）、还原性谷胱甘肽（glutathione peroxidase，GSH）、活性氧（reactive oxygen species，ROS）水平；采用TUNEL染色法观察大鼠心肌细胞凋亡情况；采用Western blotting检测心肌组织中核因子红细胞2相关因子2（nuclear factor red blood cell 2 associated factor 2，Nrf2）和血红素加氧酶-1（heme oxygenase-1，HO-1）蛋白表达。结果 与对照组比较，模型组大鼠心电图II导联ST段弓背向上抬高（P<0.01），提示急性心肌梗死模型构建成功；EF和FS显著降低（P<0.01）；血清中LDH、AST、CK-MB活性及TC、TG、LDL-C水平显著升高（P<0.01）；心肌组织中SOD、CAT、Na⁺，K⁺-ATP酶、Ca²⁺，Mg²⁺-ATP酶活性和GSH水平显著降低（P<0.01），MDA和ROS水平显著升高（P<0.01）；心肌组织出现显著的病理性改变，心肌梗死面积增加（P<0.01），心肌细胞凋亡数量显著增加（P<0.01）；心肌组织中Nrf2和HO-1蛋白表达水平显著降低（P<0.01）。与模型组比较，荆防颗粒组大鼠EF和FS显著升高（P<0.05、0.01）；血清中LDH、AST、CK-MB活性及TC、TG、LDL-C水平显著降低（P<0.05、0.01）；心肌组织中SOD、CAT、Na⁺，K⁺-ATP酶、Ca²⁺，Mg²⁺-ATP酶活性和GSH水平显著升高（P<0.05、0.01），MDA和ROS水平显著降低（P<0.05、0.01）；心肌组织病理性改变得到显著改善，心肌梗死面积和细胞凋亡数量显著降低（P<0.05、0.01）；心肌组织中Nrf2和HO-1蛋白表达水平显著升高（P<0.05、0.01）。结论 荆防颗粒通过抑制心肌细胞凋亡和氧化应激损伤从而发挥心脏保护作用。

Objective To explore the protective effect of Jingfang Granules (荆防颗粒) on isoproterenol (ISO)-induced acute myocardial infarction in rats. Methods SD rats were randomly divided into control group, model group, propranolol (10 mg/kg) group and Jingfang Granules high-, low-dose (32, 16 g/kg) groups, with 8 rats in each group. Rats in each administration group were ig corresponding drugs once a day for 14 d, 2 h after administration on 13th day, except for control group, rats in other groups were sc ISO (85 mg/kg) at multiple points, and control group was sc same volume physiological saline for two consecutive days. Electrocardiogram was used to observe the changes of ST segment. Left ventricular ejection fraction (EF) and fractional shortening (FS) were examined by echocardiography. Hearts were collected and heart weight index (HWI) was calculated. Pathological changes of myocardium were observed by hematoxylin eosin (HE) staining; Infarct size was measured by 2,3,5-triphenyltetrazolium chloride (TTC) method; Activities of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST) and levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum were detected by automatic biochemical analyzer; Activities of superoxide dismutase (SOD), catalase (CAT), Na⁺, K⁺-ATP, Ca²⁺, Mg²⁺-ATP and levels of malondialdehyde (MDA), glutathione peroxidase (GSH), reactive oxygen species (ROS) in myocardium of rats were measured by kit; TUNEL staining was used to observe the apoptosis of myocardial cells in rats; Nuclear factor red blood cell 2 associated factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions in myocardium were detected by Western blotting. Results Compared with control group, ST segment in lead II of Electrocardiogram in model group was elevated upward (P < 0.01), indicating that the model of acute myocardial infarction was successfully constructed; EF and FS were significantly decreased (P < 0.01); Activities of LDH, AST, CK-MB and levels of TC, TG, LDL-C in serum were significantly increased (P < 0.01); Activities of SOD, CAT, Na⁺, K⁺-ATPase, Ca²⁺, Mg²⁺-ATPase and level of GSH in myocardium were significantly decreased (P < 0.01), while the levels of MDA and ROS were increased (P < 0.01); Myocardial tissue showed significant pathological changes, myocardial infarction area was increased (P < 0.01), apoptosis of myocardial cells were significantly increased (P < 0.01); Nrf2 and HO-1 protein expressions in myocardium were significantly decreased (P < 0.01). Compared with model group, EF and FS in Jingfang Granules group were significantly increased (P < 0.05, 0.01); Activities of LDH, AST, CK-MB and levels of TC, TG, LDL-C in serum were decreased (P < 0.05, 0.01); Activities of SOD, CAT, Na⁺, K⁺-ATP, Ca²⁺, Mg²⁺-ATP and level of GSH in myocardium were significantly increased (P < 0.05, 0.01), while the levels of MDA and ROS were significantly decreased (P < 0.05, 0.01); Pathological changes of myocardial tissue were significantly improved, myocardial infarction area and apoptosis of myocardial cells were significantly reduced (P < 0.05, 0.01); Nrf2 and HO-1 protein expressions in myocardium were significantly increased (P < 0.05, 0.01). Conclusion Jingfang Granules can protect the heart by inhibiting apoptosis of myocardial cells and oxidative stress injury.

R285.5

荆防颗粒二次开发（2180071720113）