摘要
目的:探讨非酒精性脂肪性肝炎形成阶段肠黏膜屏障的损伤情况。方法:24只雄性Wistar大鼠随机分为对照组(普通饮食)和模型组(高脂饮食),各组12只。8周、12周处死大鼠后称量体重、肝重,并计算肝指数,检测血清甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、肿瘤坏死因子(TNF-α)水平及门静脉、腹主动脉血中内毒素(ET)水平;取小肠组织经透射电镜观察其超微结构的改变;取肝标本做HE染色,观察其病理变化。结果:8周、12周模型组大鼠肝指数与同期对照组相比差异有显著性意义(P<0.01);8周模型组大鼠TG、ALT与同期对照组比较呈升高趋势,12周差异有统计学意义(P<0.05);8周、12周模型组大鼠血清TNF-α水平与同期对照组比较明显升高(P<0.05);8周、12周模型组大鼠门静脉ET水平较对照组明显上升(P<0.05);腹主动脉血ET与同期门静脉ET比较,差异有显著性意义(P<0.05);8周、12周观察模型组大鼠小肠组织病理学变化,发现肠上皮细胞变性、坏死、脱落,并有炎细胞浸润;透射电镜显示肠上皮连接增宽,绒毛稀疏、缺如,固有层水肿。结论:非酒精性脂肪性肝炎发生时伴有肠源性内毒素血症(IETM)的形成,IETM可促使炎症因子TNF-α释放增加,加重肝脏损害,IETM的形成与肠黏膜屏障受损有关。
Objective： To elucidate the mechanism of intestinal mucosa injuries in nonalcoholic steatohepatitis （ NASH ） induced by high-fat diet. Methods： Twenty-four male Wistar rats were divided randomly into the following 2 groups： （1） control group given a standard chow, （2） model group given high-fat diet （88% standard chow ＋ 10 % lard ＋ 2% cholesterol） . The two groups of rats were executed at 8 wk and 12 wk respectively. The body weight and liver weight were weighed. Then, the liver index were calculated. The levels of serum TG, ALT, TNF-α and endotoxin were detected in the abdominal aorta at 8 wk and 12 wk respectively. Then, the level of endotoxin was detected in the portal vein at 8 wk and 12 wk respectively. The ultra-structures of small intestine were observed by transmission electron microscope. The specific tissue of liver was fixed in 10% buffered formalin, processed and embedded in paraffin for hematoxylin eosin （H＆E） . Results： The liver index in the model group were significantly higher than that in the control group （P 〈0.01 ） . The level of TG and ALT in the model group were not significantly higher than that in the control group at 8 wk. （P 〉0. 05） . But at 12 wk, they were significantly higher （P 〈0. 05） . The level of TNF-α in the model group were significantly higher than that in the control group （ P 〈 0. 05 ） . At 8 wk and 12 wk, endotoxin levels in the portal vein of model group were significantly increased compared with control group （ P 〈 0. 05 ） . Endotoxin levels in abdominal aorta and in the portal vein of the same time were significantly different （ P 〈 0. 05 ） . Histological observation showed degeneration, necrosis, loss of intestinal epithelial cells and infiltration of inflammatory cells. Transmission electron microscope revealed that intestinal epithelial connections were widened, the microvilli were sparse, absent and the lamina propria was edematus. Conclusion： NASH is accompanied with IETM. IETM leads to the level of TNFα increasing in the liver, which can aggratate liver damage. IETM forming is related to intestinal mucosa injuries.
出处
《中西医结合肝病杂志》
CAS
2009年第2期95-97,共3页
Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
基金
山西省科学技术发展计划项目(2007031092-1)
山西医科大学学生创新项目基金资助项目(200410)
