硫化氢对肝纤维化大鼠肝脏Ⅰ、Ⅲ型胶原表达的影响

Hydrogen sulfide decreases collagen Ⅰ and collagen Ⅲ expression in the liver of rats with experimental hepatic fibrosis

目的:探讨硫化氢(hydrogen sulfide,H2S)对肝纤维化大鼠肝脏Ⅰ型胶原(COL-Ⅰ)和Ⅲ型胶原(COL-Ⅲ)的影响.方法:选择硫氢化钠(sodium hydrosulfide,NaHS)作为H2S的供体,将32只♀SD大鼠分为3组:正常组(N组)8只、肝纤维化组(hepatic fibrosis,HF组)13只、NaHS干预组(S组)11只,采用四氯化碳复合因素法复制肝纤维化模型,S组自造模第6周始给予NaHS56μmol/(kg·d)腹腔注射12d,N组和HF组给予同等剂量的生理盐水腹腔注射.干预结束后,宰杀大鼠留取肝脏行肝组织病理切片HE染色评价肝纤维化分期,行Masson染色观察胶原纤维沉积情况,应用RT-PCR法检测肝脏中COL-Ⅰ、COL-ⅢmRNA表达,采用SP免疫组织化学法检测肝脏COL-Ⅰ、COL-Ⅲ表达.结果:HF组与N组相比,COL-Ⅰ、COL-Ⅲ及其mRNA表达升高(均P=0.000),与肝纤维化分期结果一致(P=0.000);S组与HF组相比,COL-Ⅰ和COL-Ⅲ表达降低(均P=0.000);COL-ⅠmRNA表达降低(P=0.009),同时COL-ⅢmRNA表达亦降低(P=0.003),肝纤维化分期下降(P=0.047).结论:H2S具有降低肝脏Ⅰ、Ⅲ型胶原表达的作用,能够延缓肝纤维化的发生发展.

AIM：To investigate the effect of hydrogen sulfide on collagen Ⅰ and collagen Ⅲ expression in the liver of rats with experimental hepatic fibrosis.METHODS：Thirty-two female SD rats were randomly divided into three groups：normal control group,hepatic fibrosis group,and hydrogen sulfide group.Rats in the hepatic fibrosis group and hydrogen sulfide group were subcutaneously injected with carbon tetrachloride to induce hepatic fibrosis.Rats in the hydrogen sulfide group were intraperitoneally injected with sodium hydrosulfide（56μmol/kg·d;the donor of hydrogen sulfide）.Fibrosis was staged using histopathological methods.The expression of collagen Ⅰ and collagen Ⅲ was detected by immunohistochemistry and RT-PCR.RESULTS：Compared to the normal control group,the stage of fibrosis was elevated（P0.01） and the expression of collagen Ⅰ and collagen Ⅲ was increased（both P0.01） in the hepatic fibrosis group.Compared to the hepatic fibrosis group,the stage of fibrosis declined（P0.05） and the expression of collagen Ⅰ and collagen Ⅲ was decreased（both P0.01） in the hydrogen sulfide group.CONCLUSION：Hydrogen sulfide can decrease the expression of collagen Ⅰ and collagen Ⅲ and inhibit the progression of hepatic fibrosis in rats.