瘦素预处理经P13KAKT及mTOR信号通路对大鼠心肌缺血-再灌注损伤的保护作用  

Protective effect of Leptin pretreatment via PI3K/AKT/mTOR signaling pathway on myocardial ischemia reperfusion injury in rats

作　　者：王文艳[1] 徐彤彤[1] 曾文轩 戴春光[2] 

机构地区：[1]桂林医学院附属医院特需病区,广西桂林541001 [2]桂林医学院附属医院重症科

出　　处：《中国急救医学》2016年第2期155-158,I0001,共5页Chinese Journal of Critical Care Medicine

摘　　要：目的观察瘦素预处理（1eptin）在大鼠心肌缺血-再灌注中对磷脂酰肌醇3-激酶（P13K）、蛋白激酶B（AKT）及雷帕霉素靶蛋白（mTOR）信号通路的调控，从抗凋亡途径探讨其保护作用。方法SPF级健康成年雄鼠80只，随机分为I／R组、Sham组、L—Lep＋IfR组（20μg／kg）、M—Lep＋I／R组（50μg/kg）和H—Lep＋I／R组（100μg/kg）。术后观察24h所有实验大鼠，分离心脏组织，HE染色分析病理变化，蛋白印迹技术检测P13K、AKT及mTOR蛋白的水平。结果与Sham组比较，I／R组及Lep＋I／R三组的HE染色均表现为明显的心肌纤维紊乱、炎症细胞浸润及红细胞渗出，且P13K、AKT和rnTOR的表达量比较差异均有统计学意义（P〈0．05）；与I／R组比较，Lep＋I／R组的HE染色病理改变明显改善，P13K、AKT和mTOR表达量均有不同程度的增高，且差异有统计学意义（均P〈0．05）。结论瘦素预处理对大鼠心肌缺血-再灌注有保护作用，其作用机制可能与瘦素上调心肌组织中P13K、AKT和mTOR表达，促进心肌细胞生存，抑制细胞凋亡有关。Objective To investigate the protective effect of leptin on myocardial ischemia reperfusion injury in rats and whether it is through the regulation of PI3K/AKT/mTOR signaling pathway. Methods Eighty SPF healthy adult male rats were randomly assigned to I / R group, Sham group, L -Lep ＋I/R group （20 μg/kg） , M - Lep ＋ I/R group （50μg/kg） , H - Lep ＋ I/R group （ 100 μg/kg）. After 24 h, heart tissue was sampled. HE staining was used to analyze the pathological changes and Western blot was used to test the level of PI3K, AKT and mTOR protein. Results Compared with Sham group, the lie staining of the other three groups （I/R group and Lep ＋ I/R groups） showed obvious myocardial fibrosis, inflammatory cell infiltration, red blood cell exudation, and AKT, roTOR, PI3K expression were significantly different （P 〈 0.05）. Compared with I/R group, HE staining in Lep ＋ I/R group was significantly improved, AKT, mTOR, PI3K expression increased, and the difference was statistically significant （P 〈 0.05）. Conclusion Leptin pretreatment has protective effect on myocardial isehemia reperfusion in rats. The possible mechanism might be related to leptin upregulating the expression of PI3K, AKT and mTOR proteins in myocardium tissue, then promoting myocardial cell survival and inhibiting cell apoptosis.

关 键 词：瘦素预处理 心肌缺血-再灌注损伤(MIRI) 磷脂酰肌醇3-激酶(PI3K) 蛋白激酶B(AKT) 雷帕霉素靶蛋白(mTOR) 

分 类 号：R542.2[医药卫生—心血管疾病]