摘要
目的观察没食子儿茶素没食子酸酯(EGCG)对大鼠心肌缺血再灌注损伤(ischemia-reperfusion injury,IRI)的保护作用,并探讨其作用机制。方法建立大鼠急性心肌缺血再灌注(I/R)模型,将大鼠分为假手术组(SO组)、I/R组和EGCG组。EGCG组(10mg/kg)在再灌注开始前5min予以静脉滴注。采用心电图记录仪观察I/R过程中室性心律失常发生频次并评分,检测大鼠血清中心肌酶学〔乳酸脱氢酶(LDH)和肌酸激酶(CK)〕水平,心肌组织中炎症因子〔肿瘤坏死因子-α(TNF-α)、白介素-6和白介素-8(IL-6和IL-8)〕的表达,心肌组织HE染色进行病理学观察,Western blot检测磷脂酰肌醇3-激酶(phosphatidyl inositol 3-kinase,PI3K)/蛋白激酶B(Akt)通路蛋白中磷酸化的PI3K调节亚基(p-p85)和Akt蛋白(p-Akt)表达水平。结果 I/R组大鼠各类室性心律失常的频次增加明显,其心律失常严重程度评分(P<0.01)、血清中LDH与CK表达水平、心肌组织中TNF-α、IL-6和IL-8的表达水平均高于SO组(P<0.05);EGCG组心律失常严重程度评分、LDH与CK的表达水平、心肌组织中TNF-α、IL-6和IL-8的表达水平均低于I/R组(P<0.05),并且EGCG组大鼠心肌病理学损伤程度轻于I/R组,EGCG组大鼠心肌中p-p85与p-Akt表达水平高于I/R组(P<0.05)。结论 EGCG能通过激活PI3K/Akt信号通路抑制炎症反应水平,有效减轻IRI。
Objective This study was designed to investigate whether epigallocatechin-3-gallate（EGCG）postconditioning protects the heart against ischemic-reperfusion injury（IRI）,and to explore its potential mechanisms in a rat model.Methods Male Wistar rats were subjected to myocardial ischemia（30 min）and reperfusion（up to 2h）and the rats were divided into sham group（SO）group,ischemia-reperfusion（I/R）model group and EGCG group.EGCG group were treated with EGCG（10mg/kg）via intravenous infusion 5min before reperfusion.Electrocardiogram were applied to record ventricular arrhythmia frequency.The severity of myocardial injury〔serum level of lactate dehydrogenase（LDH）and creatine kinase（CK）,hematoxylineosin（HE）staining〕and ventricular arrhythmia,and the serum levels of inflammatory cytokines 〔tumor necrosis factor-α（TNF-α）,interleukins-6（IL-6）and IL-8〕were assessed with ELISA,electrocardiogram and Western blot respectively.Results EGCG given before reperfusion could effectively reduce the serum level of LDH and CK and the incidence of ventricular arrhythmia（P〈0.05,respectively）,improved the pathological damage.Meanwhile,EGCG could down-regulate the expression levels of TNF-α,IL-6,IL-8 in the myocardial tissue after IRI（P〈0.05,repectively）.The expression levels of p-p85 and p-Akt in the EGCG group were significantly up-regulated compared to those in I/R group（P〈0.05,repectively）.Conclusion EGCG-related anti-inflammatory action could attenuate rat myocardial IRI and this cardioprotective effect might be activated through the PI3K/Akt pathway.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2016年第3期305-309,共5页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(No.81300155)资助
