摘要
目的 探讨内毒素在非酒精性脂肪性肝炎发病中的作用。方法 通过高脂饮食建立大鼠非酒精性脂肪性肝炎(NASH)模型,并在实验第4、8、12、16、24周分批处死,同期设正常饮食组作为对照。腹主动脉采血,测定血清内毒素,肿瘤坏死因子(TNFα)和白细胞介素-1(IL-1)β水平,肝组织切片行溶菌酶、CD14免疫组织化学染色。 结果 成功建立大鼠NASH伴肝纤维化模型,NASH大鼠外周血内毒素水甲仅在24周脂肪性肝炎肝纤维化阶段明显升高为(0.23±O.06)Eu/L,对照组为(0.15±0.03)Eu/L(t>2.179,P<0.05),而4周起肝组织CD14表达就上调,溶菌酶阳性的库普弗细胞被激活,并随着实验的进展更加明显。血清TNFα水平从8周起明显增高为(26.39±24.21)pg/ml,对照组为(9.82±9.29)pg/ml(t>2.145,P<0.05),IL-1β从16周起升高为(23.76±21.81)pg/ml,对照组为(6.25±2.98)pg/ml(t>2.145,P<0.05)。 结论 NASH时存在内毒素性肝损伤。内毒素激活肝脏库普弗细胞以及促使TNFα等细胞因子释放可能是NASH的发病机制之一。
Objective To explore the role of endotoxin in the pathogenesis of nonalcoholic steatohepatitis (NASH). Methods Rat models of NASH were established by giving a fat-riched diet. These rats were sacrificed at the 4th,8th, 12th, 16th and 24th weeks during the study. The other rats fed with normal diet were taken as normal controls at the same stage during the study. The blood of abdominal aorta was obtained and the levels of serum endotoxin, tumor necrosis factor-α (TNF-α ), and interleukin-1β (IL-1β ) were measured. The expression of CD14 and lysozyme in rats' livers were detected by immunohistochemistry. Results Rat models of NASH with liver fibrosis were established successfully. The levels of endotoxin in aorta blood of NASH rats increased significantly at the 24th week (0.23 EU/L ±0.06 EU/L vs 0.15 EU/L ± 0.03 EU/L, t > 2.179, P < 0.05) while the expression of CD14 increased from the 4th week, and the Kupffer cells expressing lysozyme were activated, then kept increasing activation through the study. In NASH rats, the levels of serum TNF-α increased from the 8th week (26.39 pg/ml± 24.21 pg/ml vs 9.82 pg/ml ±9.29 pg/ml, t> 2.145, P < 0.05) and serum IL-1β increased from the 16th week (23.76 pg/ml ± 21.81 pg/ml vs 6.25 pg/ml ± 2.98 pg/ml, t > 2.145, P < 0.05). Conclusion Liver injury results from endotoxin existing in NASH rats which may play an important role in the pathogenesis of NASH by activating Kupffer cells and inducing the production of cytokines, such as TNF-α.
出处
《中华肝脏病杂志》
CAS
CSCD
2003年第2期73-76,共4页
Chinese Journal of Hepatology
基金
国家自然科学基金资助(39800O51)
上海市青年科技启明星项目(QB14010)
