内毒素诱发非酒精性脂肪性肝炎的机制  

Mechanism of endotoxin inducing nonalcoholic steatohepatitis

作　　者：刘欣[1] 韩德五[1] 郭建红[1] 郭江红[1] 赵元昌[1] 

机构地区：[1]山西医科大学肝病研究所,太原030001

出　　处：《山西医科大学学报》2010年第5期400-403,共4页Journal of Shanxi Medical University

基　　金：山西省自然科学基金资助项目(2008011073-1)

摘　　要：目的探讨肠源性内毒素血症(IETM)对高糖高脂膳食所致的非酒精性脂肪性肝炎(NASH)的作用机制。方法将24只Wistar雄性大鼠随机分为4组:4周正常对照组,4周高糖高脂组,9周正常对照组,9周高糖高脂组。测定血清中丙氨酸氨基转移酶(ALT)、内毒素(LPS)、肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)、脂联素(APN)、空腹血糖(FPG)、空腹胰岛素(FINS),并计算胰岛素抵抗指数(IRI)。肝脏切片HE染色,观察肝脏组织学变化。结果与正常对照组相比,4周和9周高糖高脂组的大鼠血清ALT、LPS、TNF-α、FPG、FINS和IRI的水平都升高,而APN和IL-10的水平降低,4周的结果差异能看出变化的趋势但无统计学意义,9周的结果差异有统计学意义(P<0.05)。结论高糖高脂饮食可诱导大鼠发生严重的NASH以及早期糖尿病,其机制可能是与LPS引发的胰岛素抵抗以及TNF-α、IL-10和APN等因子水平失衡和相互作用有关。Objective To investigate the role of intestinal endotoxemia（IETM）in nonalcoholic steatohepatitis（NASH）induced by high-sucrose and high-fat diet. Methods Twenty-four male Wistar rats were randomly divided into four groups：4 week control group,9 week control group,4 week high-sucrose and high-fat group,9 week high-sucrose and high-fat group.The levels of alanine transaminase（ALT）,endotoxin,tumor necrosis factor-α（TNF-α）,interleukin-10（IL-10）,adiponectin（APN）in the serum,fasting plasma glucose（FPG）,fasting plasma insulin（FINS） were measured,and the insulin resistance index（IRI）was calculated.The histological changes of liver tissues were observed by HE. Results Compared with normal control groups,the levels of ALT,endotoxin,TNF-α,IL-10,FPG,FINS and IRI in the serum of rats increased in high-sucrose and high-fat groups（P〈0.05 in 9 week group）,but the levels of APN and IL-10 reduced（P〈0.05 in 9 week group）. Conclusion NASH and diabetes mellitus in rats can be induced by high-sucrose and high-fat diet,which may be related to the endotoxin-induced insulin resistance and the imbalance and interaction between some factors such as TNF-α,IL-10 and APN.

关 键 词：内毒素 胰岛素抵抗 非酒精性脂肪性肝炎 

分 类 号：R575.1[医药卫生—消化系统]