内毒素在NASH发展为肝纤维化中的作用

Role of endotoxin in NASH developing hepatic fibrosis

目的探讨肠源性内毒素血症(IETM)在非酒精性脂肪性肝炎(NASH)发展为肝纤维化中的作用。方法将24只SD大鼠随机分为4组:3个月正常对照组,3个月高糖高脂组,6个月正常对照组,6个月高糖高脂组。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)、单核细胞趋化蛋白-1(MCP-1)、空腹血糖(FPG)、空腹胰岛素(FINS),并计算胰岛素抵抗指数(IRI),以及肝匀浆羟脯氨酸(HYP);肝脏切片HE染色及VanGieson染色,观察肝脏组织学变化。结果与正常对照组相比,高糖高脂组大鼠的ALT、LPS、TNF-α、MCP-1、FPG、FINS和IRI的水平都升高,其差异均有统计学意义(P<0.05);与3个月高糖高脂组相比,6个月高糖高脂组的大鼠肝组织匀浆HYP的水平升高(P<0.05)。结论 LPS在NASH发展为肝纤维化过程中发挥着重要作用,其机制可能是LPS可激活脂肪组织中的脂肪细胞释放大量促纤维化细胞因子(如TNF-α),从而启动并促进肝脏纤维化的发生发展。

Objective To investigate the role of intestinal endotoxemia（IETM）in nonalcoholic steatohepatitis（NASH）developing hepatic fibrosis. Methods Twenty-four SD rats were randomized into four groups：3 month control group,6 month control group,3 month high-sucrose and high-fat group,6 month high-sucrose and high-fat group.The levels of alanine transaminase（ALT）,endotoxin,tumor necrosis factor（TNF-α）,monocyte chemoattractant protein-1（MCP-1）in the serum,fasting plasma glucose（FPG）,fasting plasma insulin（FINS）were measured,the insulin resistance index（IRI）was calculated,and hydroxyproline（HYP）in hepatic homogenate was exa-mined.The histological changes of liver tissues were observed by HE and VG. Results Compared with normal control groups,the levels of ALT,endotoxin,TNF-α,MCP-1,FPG,FINS and IRI in the serum increased in high-sucrose and high-fat groups（P0.05）.Compared with 3 month high-sucrose and high-fat group,the HYP level in hepatic homogenate increased in 6 month high-sucrose and high-fat group （P0.05）. Conclusion Endotoxin plays a very important role in the process of NASH developing into fibrosis,which may be caused by LPS activating the adipocytes in adipotic tissue to release lots of profibrotic cytokines（e.g.TNF-α）.