论文部分内容阅读
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 To observe the protective effect of gallocatechin gallate (EGCG) on myocardial ischemia-reperfusion injury (IRI) in rats and its mechanism. Methods A rat model of acute myocardial ischemia / reperfusion (I / R) was established. The rats were divided into sham operation group (SO group), I / R group and EGCG group. The EGCG group (10 mg / kg) was given intravenously 5 minutes before reperfusion. The frequency and severity of ventricular arrhythmia during I / R were observed by electrocardiograph. Serum levels of myocardial enzymes (lactate dehydrogenase (LDH) and creatine kinase (CK)) were measured. The levels of inflammatory cytokines The expressions of TNF-α, IL-6 and IL-8 were detected by immunohistochemistry and the pathological changes of myocardium were observed by HE staining. The levels of phosphatidylinositol 3-kinase phosphorylation of PI3K regulatory subunit (p-p85) and Akt protein (p-Akt) in phosphatidylinositol 3-kinase (PI3K) / protein kinase B (Akt) pathway proteins. Results The frequency of various types of ventricular arrhythmias in I / R rats increased significantly, and the severity of arrhythmia (P <0.01), the levels of LDH and CK in serum, the levels of TNF-α, IL-6 and IL -8 were significantly higher than those in SO group (P <0.05). The severity of arrhythmia, expression of LDH and CK in EGCG group and expression of TNF-α, IL-6 and IL-8 in myocardium were lower (P <0.05), and the degree of myocardial pathological damage in EGCG group was less than that in I / R group. The expression of p-p85 and p-Akt in EGCG group was higher than that in I / R group P <0.05). Conclusion EGCG can effectively reduce the IRI by inhibiting the PI3K / Akt signaling pathway and inhibiting the inflammatory response.