榅桲总黄酮对心肌梗死大鼠心肌损伤的保护作用及对JNK和NF-κB通路的影响

Protective effects of total flavonoids of Cydonia Oblonga Mill on myocardial injury in myocardial infarction in rats and its effect on JNK and NF-κB pathway

目的探究榅桲总黄酮(COMF)对心肌梗死大鼠心肌损伤的保护作用及机制。方法构建急性心肌梗死大鼠模型,随机分为5组,每组20只,sham组和模型组灌胃给蒸馏水10μL/g;阿托伐他汀钙片(ACT)组灌胃给予ACT 8mg/kg;榅桲总黄酮低剂量组(L-COMF)和榅桲总黄酮高剂量组(H-COMF)组分别灌胃给予榅桲总黄酮80μg/g和160μg/g,连续给药3周。氯化三苯基四氮唑红(TTC)染色法检测心肌梗死面积;血流动力学检测心功能;苏木精-伊红(HE)染色检测组织学变化;TUNEL法检测心肌细胞凋亡;酶链免疫吸附试验(ELISA)检测肿瘤坏死因子(TNF)-α、单核细胞趋化蛋白-1(MCP-1)水平;Western blot分析核因子(NF)-κB和丝裂原活化蛋白激酶(MAPKs)活性。结果与sham组相比,模型组大鼠心肌梗死面积、TUNEL阳性细胞数、TNF-α和MCP-1水平、NF-κB、p-ERK1/2、p-C-Jun N-末端激酶(JNK)、p-p38 MAPK、Bax蛋白表达显著升高,Bcl-2蛋白表达显著降低(P<0.05)。与模型组相比,ACT组、L-COMF组、H-COMF组大鼠心肌梗死面积、TUNEL阳性细胞数、TNF-α和MCP-1水平、NF-κB、p-JNK、Bax蛋白表达显著降低,Bcl-2蛋白表达显著升高(P<0.05)。与sham组相比,模型组大鼠平均动脉压(MAP)、左心室收缩压(LVSP)显著降低,左心室舒张末压(LVEDP)显著升高,同时左心室内压上长最大速率(LV+dp/dtmax)显著降低,左心室内压下降最大速率(LV-dp/dtmax)显著升高(P<0.05)。与模型组相比,ACT组、L-COMF组、HCOMF组大鼠MAP、LVSP显著升高,LVEDP显著降低,同时LV+dp/dtmax显著升高,LV-dp/dtmax显著降低(P<0.05)。结论榅桲总黄酮能够对心肌梗死大鼠心肌损伤发挥保护作用,这可能是通过抑制JNK和NF-κB信号通路,从而下调心肌梗死引起的炎症损伤和细胞凋亡来实现的。

Objective To investigate the protective effect of total flavonoids of Cydonia Oblonga Mill(COMF)on myocardial injury in myocardial infarction in rats and its possible mechanism.Methods Rat model of acute myocardial infarction was established and randomly divided into 5 groups,20 rats in each group.The sham group and model group were given the intragastric administration of distilled water 10μL/g.The atorvastatin calcium tablets(ACT)group was given orally atorvastatin 8 mg/kg.The low-dose COMF(L-COMF)group and high-dose COMF(H-COMF)group were given COMF as 80μg/g and 160μg/g respectively,continuous intragastric administration for 3 weeks.The area of myocardial infarction was determined by TTC staining.And cardiac function was determined by hemodynamic detection.Histological changes were detected by hematoxylin-eosin(HE)staining.TUNEL assay was used to detect the apoptosis of myocardial cells.Enzyme chain immunosorbent assay(ELISA)was used to detect the tumor necrosis factor-α(TNF-α)and monocyte chemokine protein-1(MCP-1)levels.Western blot was performed to analyze the activities of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPKs).Results Compared with the sham group,area of myocardial infarction,TUNEL positive cells,TNF-αand MCP-1,NF-κB,p-ERK1/2,p-JNK,p-p^38 MAPKs,Bax expression in the ACT,L-COMF and H-COMF group significantly increased,Bcl-2 protein expression significantly decreased(P<0.05).Compared with the model group,area of myocardial infarction,TUNEL positive cells,TNF-αand MCP-1,NF-κB,p-ERK1/2,p-JNK,Bax expression in the ACT,L-COMF and H-COMF group significantly decreased,Bcl-2 protein expression significantly increased(P<0.05).Compared with the sham group,mean arterial pressure(MAP),left ventricular systolic pressure(LVSP)and LV+dp/dtmax significantly decreased,while LV-dp/dtmax were significantly increased(P<0.05).Compared with the model group,MAP,LVSP and LV+dp/dtmax significantly increased,while LVEDP and LV-dp/dtmax significantly decreased(P<0.05).Conclusion COMF plays a protective role in the myocardial injury of myocardial infarction rats,which may be through inhibition of JNK and NF-κB signaling pathways and down-regulating the inflammatory injury and cell apoptosis induced by myocardial infarction.