小剂量内毒素预处理对大鼠心肌缺血再灌注损伤的作用及其机制  

Effect and Mechanism of Low-dose Endotoxin Pretreatment on Myocardial Ischemia Rererfusion Injury in Rats

作　　者：何川[1] 李银萍[2] 姚兰[1] 廉应涛 徐松 陆礼萍 余追[1] 

机构地区：[1]武汉大学人民医院重症医学科,武汉430060 [2]武汉大学基础医学院病理学与病理生理学系,武汉430071

出　　处：《微循环学杂志》2017年第4期29-33,共5页Chinese Journal of Microcirculation

基　　金：武汉市科技局课题(2015060101010045)

摘　　要：目的:观察小剂量内毒素(LPS)预处理对心肌缺血再灌注损伤(IRI)大鼠的作用及其机制。方法:30只健康雄性SD大鼠,随机分为假手术组(Sham组)、IRI组、内毒素各剂量(0.1mg/kg,0.5mg/kg,1mg/kg)预处理组(LPS组),每组各6只;IRI组采用结扎左冠状动脉前降支(LAD)30min、再灌注4h的方法制备心肌IRI模型;LPS各剂量组分别于术前24h腹腔注射LPS 0.1mg/kg、0.5mg/kg、1mg/kg,其余处理同IRI组;Sham组只穿线不结扎。各组分别于再灌注4h结束后下腔静脉采血并摘取心脏,HE染色观察心肌组织病理学改变,全自动生化分析仪检测血清心肌酶(LDH、AST)含量,ELISA检测血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)的表达水平。结果:与Sham组比较,IRI组大鼠血清LDH、AST、IL-1β和IL-10明显升高(P<0.01),LPS各剂量组血清LDH、AST和IL-1β均较IRI组明显降低(P<0.05或P<0.01),而LPS各剂量组间LDH、AST和IL-1β差异无统计学意义(P>0.05)。IRI组、LPS 0.1mg/kg组、LPS 1mg/kg组IL-10含量无统计学差异(P>0.05),而LPS 0.5mg/kg组IL-10含量较IRI组和LPS 0.1mg/kg组升高(P<0.05或P<0.01)。结论:小剂量LPS预处理对心肌IRI有保护作用,其机制与促进抗炎因子IL-10及抑制促炎因子IL-1β的表达有关,且该保护作用不呈剂量依赖性。Objective： To investigate the effect and mechanism of low-dose LPS pretreatment on myocardial ischemia reperfusion injury in rats. Method： Thirty male Sprague-Dawley rats were randomly divided into the follow- ing groups：sham group, ischemia-reperfusion injury group（IRI）, lipopolysaccharide （LPS） pretreatment groups： 0. lmg/kg, 0.5mg/kg and lmg/kg,6 in each group. The rats in the IRI groups were subjected to LAD occlusion for 30min follwed by reperfusion for 4h. LPS preconditioning groups were injected intraperitoneally with LPS 0. ling / kg, 0.5 mg/kg, or 1 mg/kg 24h before the surgery,and the rest operation was the same as the IRI group. While the animals in the sham group underwent surgical manipulation without ligature of the LAD. At the end of 4h reperfusion, to observe myocardial pathological changes by HE staining,the contents of myocardial enzymes（LDH,AST）were detected by automatic biochemical analyzer,and the levels of interleukin-10 （IL-10） and interleukin-1β （IL-1β） were measured by enzyme linked immunosorbent assays. Results： Compared with sham group, the serum levels of LDH,AST, IL-1β and IL-10 in IRI group were significantly higher （P〈0.01）. After pretreated with LPS, the expression levels of LDH,AST and IL-1β in each dose group were remarkably decreased than those in IRI group （P〈0.01 or P〈0.05） without substantive difference discovered between these groups（P〉0.05）. In LPS pretreatment groups, as for the IL-10 expression levels, significant differences merely existed between the pretreatment group at the dose of 0.5 mg/kg and the IRI group（P〈0.05）. Conclusion： Low dose of LPS pretreatment before myocardium suffering ischemia reperfusion injury can induce cardioprotection by promo- ting the expression of anti-inflammatory factor IL-10 and inhibiting the activation of inflammatory parameter IL-1β,and the pro-tective effect does not work in a dose-dependent manner.

关 键 词：内毒素预处理 心肌缺血再灌注损伤 心肌酶 炎症因子 大鼠 

分 类 号：R541.4[医药卫生—心血管疾病]