内毒素在非酒精性脂肪性肝炎发生发展中对过氧化物酶体增殖物激活受体α表达的影响  

Effect of Endotoxin on the expression of peroxisome proliferator-activated receptor alpha in the development of nonalcoholic steatohepatitis in rats

作　　者：李夏[1] 韩德五[1] 赵龙凤[1] 尹镭[1] 

机构地区：[1]山西医科大学肝病研究所,太原030001

出　　处：《中华肝脏病杂志》2005年第2期89-91,共3页Chinese Journal of Hepatology

基　　金：山西省高校科技研究开发项目(2003101)

摘　　要：目的 观察内毒素在非酒精性脂肪性肝炎(NASH)形成过程中对肝组织表达过氧化物酶体增殖物激活受体α(PPAR α)的影响。 方法 采用20％玉米油饲料喂饲大鼠14周建立NASH模型的同时,内毒素组于实验结束前4 h腹腔注射内毒素脂多糖(1g／L,3.0 ml／kg)1次。检测动物血浆和肝组织脂质水平以及血浆内毒素、肿瘤坏死因子、丙二醛、游离脂肪酸含量,并做病理切片。以逆转录聚合酶链反应检测大鼠肝组织PPAR α mRNA表达。 结果 腹腔注射内毒素的NASH大鼠的PPAR α表达较对照组大鼠明显下调,导致游离脂肪酸在血浆内升高[(1925.0±130.7)μmol／L],肝内甘油三酯蓄积增多[(542.7±142.8)mmol/g]。游离脂肪酸与内毒素通过肿瘤坏死因子α增高而使丙二醛增多[(4.7±1.4)μmol／ml],使肝细胞发生脂质过氧化,血浆丙氨酸氨基转移酶活性增强[(5 2.3±5.5)U／L],加重肝细胞的破坏与炎症反应。 结论 内毒素血症可下调肝组织PPAR α的表达,从而加剧肝脂变与促进脂肪性肝炎的形成。Objective To study the effect of endotoxin on the expression of peroxisome proliferator-activated receptor a (PPAR α) in the development of nonalcoholic steatohepatitis in rats. Methods A model of nonalcoholic steatohepatitis (NASH) was developed with Wistar rats fed a chow containing 20% maize oil for 14 weeks. The endotoxin group rats were intraperitoneally injected with lipopolysaccharide (LPS, I g/L, 3.0 ml/kg) once 4 hours before the end of the experiment. The concentrations of lipids, endotoxin, tumor necrosis factor- α, malondialdehyde, free fatty acid in plasma and hepatic tissues were determined and the degree of hepatocytic steatosis was studied. The expression of PPAR α mRNA in hepatic tissues was measured using reverse transcriptase-polymerase chain reaction (RT-PCR). Results The expression of PPAR α mRNA in the hepatic tissue of the LPS group was downregulated markedly in comparison to that of the control group. The level of free fatty acid and endotoxin by secreting tumor necrosis factor-α increased and triglyceride accumulated in the liver caused malondialdehyde content to increase, then lipid peroxidation process enhanced and ALT activity increased. Thus, hepatic injury and inflammatory reaction could be accelerated. Conclusion Endotoxemia can enhance hepatocellular steatosis and lead to NASH due to its downregulating the expression of PPAR α mRNA.

关 键 词：内毒素 表达 肝组织 过氧化物酶体增殖物激活受体 PPARΑ 非酒精性脂肪性肝炎 游离脂肪酸 结论 水平 目的 

分 类 号：R575.1[医药卫生—消化系统]