积雪草苷对大鼠心肌缺血再灌注损伤的保护作用以及MAPK通路的影响  

Protective effect of asiaticoside on myocardial ischemia-reperfusion injury and effect of MAPK pathway in rats

作　　者：阳飞[1] 黄辉[2] 王芳[1] 陈祖乔 杨大英[1] 周祥群[1] YANG Fei;HUANG Hui;WANG Fang;CHEN Zu-qiao;YANG Da-ying;ZHOU Xiang-qun(Department of Cardiology,Central Municipal Hospital/Third People's Hospital of Hainan Province,Hainan Sanya572000,China;Department of Cardiovascular Medicine,First Affiliated Hospital,Medical College of Shihezi University,Xinjiang Shihezi 832000,China)

机构地区：[1]三亚中心医院/海南省第三人民医院心内科,海南三亚572000 [2]石河子大学医学院第一附属医院心血管内二科,新疆石河子832000

出　　处：《中国医院药学杂志》2021年第15期1514-1518,共5页Chinese Journal of Hospital Pharmacy

基　　金：石河子大学2020年度自主资助支持校级科研立项项目(编号:ZZZC202075A)。

摘　　要：目的:研究积雪草苷对大鼠心肌缺血再灌注损伤及MAPK信号通路的影响。方法:构建大鼠心肌缺血再灌注模型,将大鼠分为对照组、模型组和积雪草苷低(12.5 mg·kg^(-1))、中(25 mg·kg^(-1))、高(50 mg·kg^(-1))治疗组。心脏超声检测心脏功能,HE染色检测心脏组织损伤程度。免疫组化检测心脏组织中ki67阳性细胞率,Western blot检测Bax、Bcl-2、磷酸化-细胞外调节激酶1/2(phosphorylation-extracellular signal-regulated kinase 1/2,p-ERK1/2)和p-p38丝裂原活化蛋白激酶(p-p38 mitogen-activated protein kinase,p-p38MAPK)的蛋白相对表达量。酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测外周血液中肌酸激酶同工酶(creatine kinase-MB,CK-MB)、肌红蛋白(myoglobin,Mb)、肌钙蛋白(cardiac troponin I,cTnI)、肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)、白介素-6(interleukin-6,IL-6)和IL-1β的蛋白相对表达量。结果:与模型组相比,在积雪草苷治疗后,大鼠心率、射血分数、左室收缩压显著上调;心肌酶Mb、cTnl、CK-MB的表达量显著下调,ki67阳性细胞率上调,促炎细胞因子IL-6、TNF-α和IL-1β的表达量下调,Bax/Bcl-2、p-ERK1/2/ERK1/2和p-p38MAPK/p38MAPK的比率显著下调。结论:积雪草苷对大鼠心肌缺血再灌注损伤的保护作用,并抑制MAPK信号通路。OBJECTIVE To explore the effects of asiaticoside on myocardial ischemia-reperfusion injury and MAPK pathway in rats.METHODS A rat model of myocardial ischemia-reperfusion was constructed.Rats were randomly divided into control group,model group and group of treatments with low(12.5 mg·kg^(-1)),medium(25 mg·kg^(-1))and high(50 mg·kg^(-1))concentrations of asiaticoside.Cardiac function was detected by echocardiography and the degree of cardiac histological injury by hematoxylin-eosin(HE)staining.Among them,ki67 cell positive rate was detected by immunohistochemistry.The protein expressive levels of Bax,Bcl-2,phosphorylation-extracellular signal-regulated kinase 1/2(p-ERK1/2)and p-p38 mitogen-activated protein kinase(p-p38 MAPK)were detected by Western blot.The levels of creatine kinase-MB(CK-MB),myoglobin(Mb),cardiactroponin I(cTnI),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1βin peripheral blood were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS Compared with model group,heart rate(HR),fraction shortening(FS)and left ventricular systolic blood pressure(LVSP)increased markedly after a treatment of asiaticoside.The expressions levels of myocardial enzymes Mb,cTnl,CK-MB were significantly down-regulated.The protein expression level of ki67 was up-regulated.In addition,proinflammatory cytokines IL-6,TNF-αand IL-1βwere down-regulated while the ratios of Bax/Bcl-2,p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK declined markedly.CONCLUSION Asiaticoside protects myocardial ischemia-reperfusion injury and inhibits the MAPK pathway in rats.

关 键 词：心肌缺血再灌注 积雪草苷 大鼠 MAPK信号通路 

分 类 号：R966[医药卫生—药理学]