干扰素α对肝纤维化鼠星状细胞Ⅰ和Ⅲ型前胶原mRNA表达及胶原沉积的影响  

Effects of interferon-α on the mRNA expression of procollagen type Ⅰ and III of hepatic stellate cells and on the deposition of collagen type I and Ⅲ in fibrotic liver of rats

作　　者：张其胜[1] 王吉耀[1] 胡美玉[1] 

机构地区：[1]上海医科大学附属中山医院消化科,200032

出　　处：《中华医学杂志》1999年第9期695-698,共4页National Medical Journal of China

基　　金：国家自然科学基金!3 95 0 0 13 8

摘　　要：目的　观察干扰素α对大鼠肝纤维化时星状细胞增殖、Ⅰ、Ⅲ型前胶原mRNA表达和肝脏胶原沉积的影响。方法　以CCl4制造肝纤维化模型 ,培养肝星状细胞 ,抽提RNA ,用地高辛标记Ⅰ、Ⅲ型前胶原和胶原酶cDNA探针 ,Northern杂交分析Ⅰ、Ⅲ型前胶原和胶原酶mRNA表达 ,Dotblot测定大鼠肝Ⅰ、Ⅲ型胶原沉积。分别用3H TdR和3H 脯氨酸掺入观察干扰素α对星状细胞增殖和胶原合成的影响。结果　干扰素α对3H TdR和3H 脯氨酸掺入的星状细胞 ,在 4、2 4、4 8小时与空白对照比较 ,呈明显抑制作用 ,其抑制率分别为 16%、19%、2 7%。干扰素α浓度≥ 12 5U/ml时呈现明显抑制作用 ,且随浓度增加抑制作用加强。在鼠肝纤维化早、中、晚期 ,干扰素α组星状细胞Ⅰ、Ⅲ型前胶原mRNA表达与模型对照组比较均降低。星状细胞间质胶原酶mRNA表达 :在模型对照组早、中期均高于正常对照组 ,而晚期与正常对照组差异无显著意义 ;在干扰素α组早、中、晚各期 ,星状细胞间质胶原酶mRNA表达与模型对照组差异无显著意义。肝内Ⅰ、Ⅲ型胶原沉积 :干扰素α组早、中期均低于模型对照组 ,而晚期与模型对照组差异无显著意义。结论　干扰素α可抑制星状细胞的增殖和胶原合成 ,下调肝纤维时Ⅰ、Ⅲ型前胶原mRNA表达 ,减少肝脏Ⅰ、Ⅲ型胶原沉积。Objective To observe the effects of interferon α on the proliferation and mRNA expression of procollagen type Ⅰ and Ⅲ and on the deposition of collagen type Ⅰ and Ⅲ in fibrotic liver of rats. Methods CCl 4 was used to induce the liver fibrosis rat model. The stellate cells were isolated from liver and cultured in DMEM medium. The effects of interferon α on the proliferation and collagen synthesis of stellate cells were determined with 3H TdR, 3H proline incorporating test. Total RNA of stellate cells was extracted and the cDNA of procollagen type Ⅰ and Ⅲ and of interstitial collagenase was labeled using Dig High Primer technique. The level of procollagen type Ⅰ and Ⅲ and interstitial collagenase mRNA were measured by Northern blot analysis. Deposition of collagen type Ⅰ and Ⅲ in fibrotic liver was evaluated with Dot blot. Resutls At the 4th, 24th and 48th hour, interferon α inhibited the intake of 3H TdR and 3H proline by stellate cells significantly. The inhibition rates were 16%, 19% and 27%, respectively. The intensity of inhibition was proportional to the concentration of interferon α. The expression level of procollagen type Ⅰ and Ⅲ mRNA in the interferon α treated group was significantly lower than that in control group in all stages of fibrosis. At the 2nd and 6th week, the deposition of collagen type Ⅰ and Ⅲ in interferon α treated group decreased significantly compared with that in control group. However, no difference was found at the 9th week. The expression of collagenase mRNA between interferon α treated group and control group showed no difference. Conclusion Interferon α can inhibid the proliferation and collagen synthesis of stellate cells, down regulate the expressions of procollagen type Ⅰ and Ⅲ mRNA and reduce the deposition of collagen type Ⅰ and Ⅲ in fibrotic liver. It has no effect on collagenase.

关 键 词：干扰素Α 肝纤维化 溶胶原 MRNA 

分 类 号：R575.2[医药卫生—消化系统]