瘦素经PI3K-AKT-NFκB通路对大鼠心肌缺血再灌注损伤的影响  

Effects of leptin via PI3K-AKT-NFκB pathway on myocardial ischemia reperfusion injury in rats

作　　者：王文艳[1] 徐彤彤[1] 曾文轩 吕祥威[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急诊科

出　　处：《临床心血管病杂志》2015年第12期1336-1339,共4页Journal of Clinical Cardiology

基　　金：广西科学研究与技术开发计划项目(桂科能:1598025-29);桂林市科学研究与技术开发计划课题(No:20130120-1);广西医疗卫生适宜技术研究与开发课题(No:S201316-03)

摘　　要：目的:观察瘦素在SD大鼠心肌缺血再灌注损伤中对磷脂酰肌醇3激酶-丝氨酸(苏氨酸)蛋白激酶B-核转录因子κB(PI3K-Akt-NFκB)信号通路的影响。方法:100只健康雄性SD大鼠随机分为A、B、C、D、E 5组(每组20只)。A组为单纯缺血再灌注模型对照组;B组为假手术组,仅开胸不作血管结扎;C、D、E组分别为瘦素低、中、高剂量干预组(剂量依次为20、50、100μg/kg)。使用线栓法制作心肌缺血再灌注模型,缺血30 min再灌注24 h后观察HE染色心肌病理学改变,蛋白印迹技术(Western Blot)观察PI3K、Akt1、NFκB蛋白的表达,酶联免疫法(ELISA)检测肿瘤刺激因子α(TNF-α)、白细胞介素-6(IL-6),观察瘦素的抗炎作用。结果:①与A组比较,C、D、E组心肌组织病理学表现均缓解,C、D、E组TNF-α、IL-6的表达较A组降低(均P<0.05),D组P13K、AKT1、NFκB表达均增加(均P<0.05),C组AKT1表达增高(P<0.05),E组PI3K、NFκB表达上调(均P<0.05);③与B组比较,A、C、D、E组心肌组织病理学变化均有差异,且TNF-α、IL-6表达均增加(均P<0.05),A组PI3K表达增加(P<0.05),C组PI3K、AKT1表达增加(均P<0.05),D、E组PI3K、AKT1、NFκB表达均增加(均P<0.05)。结论:瘦素能控制大鼠心肌缺血再灌注损伤的炎症反应,促进相关抑凋亡蛋白并维持细胞生存,其可能经PI3K-AKT-NFκB信号通路减轻心肌缺血再灌注损伤。Objective：To observe the eiiects of leptin via Phosphatidylinositol-3-kinase-Serine（1 hreonme）protein kinase B-Nuclear transcription factor κB（PI3K-AKT-NFκB） signal pathway on myocardial ischemia and reperfusion injury in SD rats.Method：A total of 100 healthy male SD rats was randomly divided into A,B,C,D,E group（n = 20）.Group A was ischemia-reperfusion model group;Group B was sham operation group,only thoracotomy without ligation;Group C,D,E respectively was in low,median,high dose leptin group（the dose was20,50,100 fig/kg respectively） Suture-occluded method was used to make the model of myocardial ischemia reperfusion injury rats.,At 24 h after 30 minutes ischemia,the pathologic changes of myocardial tissue was observed by HE staining,PI3 K,AKT1,NFkB proteins was observed by Western Blot,and the expressions of TNFa,IL-6 were tested by ELISA.Result：Compared with group A,myocardial histopathology of group C,D and E was better,and the expression of TNF-α,IL-6 was less（all P〈0.05）,the expression of AKT1,PI3 K and NFkB were increased in group D（P〈0.05）,expression of AKT1 in group C was increased（P〈0.05）,PI3 K and NFkB in group E was increased（P〈0.05）.Compared with group B,there was different pathology changes of myocardial tissue in group A,C,D and E,TNF-α and IL-6 expression of these groups all increased（all P〈0.05）,expression of PI3 K increased in group A（P〈0.05）,expression of PI3 K,AKT1 in group C increased（both P〈0.05）,though PI3 K,AKT1,NFκB all increased in group D and E（all P〈0.05）.Conclusion：Leptin can control inflammation reaction on myocardial ischemia reperfusion injury and promote the related anti apoptotic protein,then maintain cell survival,which may be possible via the PI3K-AKT-NFκB signaling pathway to alleviate myocardial ischemia reperfusion injury.

关 键 词：瘦素 心肌缺血再灌注损伤 PI3K-AKT-NFκB通路 

分 类 号：R542.2[医药卫生—心血管疾病]