肥胖对脓毒症小鼠模型的肝脏损害作用及其对炎症反应的影响  

Effects of obesity on liver injury and inflammatory response in septic mouse model

作　　者：周玉庆[1] 陈翔[1] 

机构地区：[1]重庆市急救医疗中心肝胆外科,重庆400014

出　　处：《重庆医科大学学报》2017年第12期1620-1626,共7页Journal of Chongqing Medical University

摘　　要：目的:探讨肥胖对脓毒症小鼠肝损害和炎症反应的影响。方法:6周龄C57BL/6J野生型雄性小鼠80只随机分为高脂饮食组(HFD组,40只)和普通饮食组(ND组,40只),饲养6周后称重,测葡萄糖耐量,比色法检测肝脏甘油三酯(triglyceride,TG)水平。采用盲肠结扎穿刺(cecal ligation-peferation,CLP)法构建脓毒症模型,观察小鼠生存率,取血浆和肝脏组织,HE染色观察小鼠肝脏组织,采用酶联免疫法(enzyme-linked immunosorbent assay,ELISA)检测谷丙转氨酶(alanine aminotransferase,ALT)、瘦素(leptin)、脂联素(adiponectin)、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白介素-6(interleukin-6,IL-6)及IL-10的表达,RT-PCR检测活化蛋白(activator protein-1,AP-1)mRNA的表达。结果:HFD组小鼠体质量明显重于ND组小鼠[(34.867±1.465)vs.(25.678±1.761),t=-9.827,P=0.000],负荷实验示:HFD组与ND组相比,血糖水平更高(F=200.921,P=0.000),肝脏甘油三酯水平更高(t=31.793,P=0.000)。肥胖小鼠相对于普通饮食小鼠脓毒症时生存率更低,生存时间更短(P=0.037)。经CLP处理后,肥胖小鼠血浆瘦素水平仍明显高于非肥胖小鼠[(27.64±5.16)vs.(7.12±2.91)ng/mL,F=95.141,P=0.000],而脂联素在肥胖小鼠脓毒症时表达降低[6 h ND组vs.HFD组:(8 445.344±3 245.632)vs.(2 434.532±2.012),t=2.660,P=0.000]。脓毒症时小鼠血浆TNF-α、IL-6、IL-10表达均增加[TNF-α:(2.017±1.071)vs.(170.698±37.705),t=8.137,P=0.001;(2.760±0.853)vs.(122.080±19.520),t=13.553,P=0.000;IL-6:(19.955±3.500)vs.(404.752±50.701),t=18.070,P=0.000;(15.975±4.022)vs.(533.064±104.866),t=11.032,P=0.000;IL-10:(79.810±7.042)vs.(277.156±124.213),t=4.335,P=0.012;(120.678±7.172)vs.(214.111±85.322),t=3.925,P=0.020],但肥胖小鼠相对非肥胖小鼠TNF-α和IL-10表达降低[TNF-α:(170.698±37.705)vs.(122.080±19.520),t=0.981,P=0.356;IL-10:(277.156±124.213)vs.(214.111±85.322),t=3.216,P=0.031]。血浆ALT的水平在肥胖的脓毒症小鼠中明显高于非肥胖的脓毒症小鼠[(132.77Objective：To explore the role of obesity in sepsis-induced liver injury and inflammation.Methods：The experimental groups consisted of 80 male C57 BL/6 mice at 6 weeks of age.Animals were randomized to HFD（n=40）or ND（n=40）for 6 weeks,then they were weighed.Glucose tolerance tests were measured.The liver triglyceride levels were determined by colorimetric assay kit.Poly microbial sepsis was induced by cecal ligation-peferation（CLP） and mice were monitored for survival.Plasma and liver tissues were collected.HE staining was used to observe the liver tissue of mice.The levels of alanine aminotransferase（ALT）,leptin,adiponectin,TNF-α,IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay（ELISA）.RT-PCR was used to detect the expression of activator protein-1 expression.Results：The body weight of HFD group was significantly higher than that of ND group[（34.867±1.465）vs.（25.678±1.761）,t=-9.827,P=0.000].Glucose tolerance test：compared with the ND group,the HFD group had higher blood glucose levels and higher hepatic triglyceride levels（F=200.921,P=0.000;t=31.793,P=0.000）.Obese mice had a lower survival rate and a shorter survival time（P=0.037）than ND mice in sepsis.After CLP treatment,the levels of plasma leptin in obese mice were still significantly higher than those in non-obese mice [（27.64 ±5.16） ng/mL vs.（7.12 ±2.91） ng/mL,F =95.141,P=0.000],while adiponectin expressions were decreased in obese mice[6 h ND group vs.HFD group：（8 445.344±3 245.632）vs.（2 434.532±2.012）,t=2.660,P=0.000].The expressions of TNF-α,IL-6 and IL-10 were increased in septic mice[TNF-α：（2.017±1.071）vs.（170.698±37.705）,t=8.137,P=0.001;（2.760±0.853）vs.（122.080±19.520）,t=13.553,P=0.000;IL-6：（19.955±3.500）vs.（404.752±50.701）,t=18.070,P=0.000;（15.975±4.022）vs.（533.064±104.866）,t=11.032,P=0.000;IL-10：（79.810±7.042）vs.（277.156±124.213）,t=4.335,P=0.012;（120.678±7.172）vs.（214.111±85.322）,t=3.925,P=0.020],but

关 键 词：脓毒症 肥胖 肝损害 炎症反应 

分 类 号：R575.1[医药卫生—消化系统]