Hepcidin在大鼠酒精性肝病发生发展中的作用

Effect of Hepcidin on the Development of Alcoholic Liver Disease in Rats

目的构建大鼠酒精性肝病动物模型,探讨Hepcidin在酒精性肝病发生发展中的作用。方法健康SD大鼠40只,随机分为两组,每组20只。对照组和模型组分别用生理盐水〔10 mL/(kg·d)〕和56%酒精〔10 mL/(kg·d)〕灌胃,连续12周。检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及铁含量,肝组织超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量,RT-PCR检测肝Hepcidin mRNA的表达,取大鼠肝组织行HE染色、免疫组化、苏丹染色。结果模型组大鼠血清ALT、AST及铁含量高于对照组(P<0.01),肝组织SOD活力低于对照组、MDA含量高于对照组(P<0.01)。模型组大鼠肝肿大,表面粗糙呈灰黄色,肝细胞大量变性坏死,胞质内可见大量脂滴空泡,脂肪变细胞所占比例高于对照组(P<0.05)。肝组织苏丹染色,对照组大鼠肝组织见极少量的肝细胞胞浆内橘红色染色,模型组大鼠肝细胞内见大量大小不等的橘红色染色。肝组织肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的阳性表达率模型组高于对照组(P<0.01)。半定量RT-PCR结果显示模型组大鼠肝组织Hepcidin mRNA的表达低于对照组(P<0.01)。结论酒精性肝病大鼠肝组织TNF-α、IL-6表达增加,但Hepcidin mRNA的表达下降。

Objective To establish an alcoholic liver disease model in rats to study the effect of Hepcidin on the development of alcoholic liver disease. Methods Fourty SD rats were randomly divided into 2 groups, 20 for each group. Saline[10 mL/（kg · d）] and 56% ethano infusion [10 mL/（kg · d）] were given orally to the rats for 12 weeks for the control and experimental group, respectively. The serum ALT, AST, and iron, and the superoxide dismutase （SOD） activity and malonaldehyde （MDA） content in the hepatic tissue were determined. RT-PCR was employed to examine the expression of Hepeidin mRNA in the liver. The histopathological changes of the liver tissues were examined through HE, Sudan Ⅳ and immunohistoehemieal stainings. Results The rats in the experimental group had greater serum ALT, AST and iron, and decreased SOD activity and increased MDA activity than those in the control group （P〈0.01）. The rats in the experimental group had enlarged livers, with rough surface and grey-yellow color. The rats in the experimental group had more local hepatocellular necrosis, inflammatory cells, and large fat droplets, and larger red tangerine staining sectors in the livers than those in the control group （P〈0.05）. Higher positive expressions of TNF-α and IL-6 in the liver tissues were found in the experimental group than in the control group （P〈0. 01）. The rats in the experimental group had lower levels of mRNA of Hepcidin than those in the control group（P〈0.01）. Conclusion The rats with alcoholic livers have increased expression of TNF-α and IL-6 and decreased expression of Hepcidin in the liver tissues.