文档介绍：TNFα、Leptin-Rb、NF-κB和PPAR-γ在酒精性肝病大鼠肝细胞中的表达
【摘要】目的探讨TNFα、NF-κB、Leptin-Rb和PPAR-γ等在大鼠酒精性肝病中与肝组织炎症、坏死和纤维化的关系。方法胃造瘘法建立长期大鼠酒精性肝病模型,分别在第4、8、12、24和52周用免疫组化、原位杂交和RT-PCR技术检测不同阶段大鼠肝组织中TNFα、NF-κB、PPAR-γ和Leptin-Rb等的表达。结果 TNFα、NF-κB和Leptin-Rb水平在模型组大鼠肝细胞中,第8周表达逐渐增强,第24周起高水平表达一直持续至52周(P<)。PPAR-γ在对照组和第4、8周模型组肝细胞中表达最强,第12周表达开始减弱。TNFα和NF-κB在肝细胞中的表达呈明显正相关关系,与PPAR-γ则呈负相关关系(P<)。结论 TNFα和NF-κB与肝细胞病变程度有很好的一致性关系,Leptin-Rb在肝细胞的表达与肝纤维化发展相一致,PPAR-γ则刚好相反。
【关键词】酒精性肝病细胞因子大鼠
ABSTRACT: Objective To investigate the expressions of TNFα, NF-κB, leptin-Rb and PPAR-γ mRNA in liver tissues of rats with alcoholic fatty liver to identify the relationship between these factors and liver inflammation, necrosis and fibrosis. Methods Long-time rat model groups (gastric cannulation ethanol infusion models of ALD) were made. At the end of 4th, 8th, 12th, 24th and 52th week, the expressions of TNFα, NF-κB and PPAR-γ protein and mRNA in rat liver tissues were observed with immunohistochemical method and in situ hybridization. Reverse transcription polymerase chain reaction was performed to determine the expression of Leptin-Rb mRNA. Results The expressions of TNFα, NF-κB and leptin-Rb in rat alcoholic fatty liver enhanced gradually from week 8. Strong positive expression lasted from week 24 to week 52. The expression of PPAR-γ was strongly positive in control group and in 4th and 8th week model groups (P<). The expression weakened from week 12. The expression of TNFα in liver tissues was positively correlated with that of NF-κB significantly and negatively correlated with that of PPAR-γ. Conclusion TNFα and NF-κB were strongly positively correlated with the liver inflammation and necrosis. The expression of leptin-Rb increased in hepatocytes, which induced hepatic fibrosis in rats. The expression of PPAR-γ increased in the initial period and lowered in the later time.
KEY WORDS: alcoholic fatty liver; cytokine; rats
肿瘤坏死因子-α(tumor necrosis factor-α, TNFα)是一种早期反应的细胞因子,在损伤初期即开始诱导其他促炎及抗炎