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白介素-10对肝纤维化大鼠星状细胞EGF及HGF表达的影响 被引量:5

Effect of IL-10 on the expression of EGF and HGF of HSC of hepatic fibrosis rat
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摘要 目的探讨IL10干预对实验性肝纤维化大鼠肝星状细胞EGF、HGF表达的影响及其抗纤维化作用的可能机制。方法60只♂SD大鼠随机分为正常对照组(N组,8只)、肝纤维化模型组(C组,28只)和IL10干预组(I组,24只),分别于CCl4造模第7周及11周采用链霉蛋白酶E、Ⅳ型胶原酶经门静脉灌注分离肝星状细胞。半定量RTPCR法检测各组新分离肝星状细胞中EGF、HGFmRNA表达水平;SP免疫细胞化学法检测各组原代培养3天后肝星状细胞EGF的表达。并于上述两个时间段分别将各组肝组织行HE染色判断炎症和肝纤维化程度。结果成功建立大鼠肝纤维化模型和分离大鼠肝星状细胞。与正常组相比,纤维化模型组EGF、HGF的mRNA水平显著升高(P<001),经IL10干预后则明显降低(P<001)。对EGF而言,IL10组表达量高于正常组(P<005);对HGF而言,IL10组皆低于正常组(P<005)。肝纤维化模型组EGFmRNA水平在第11周较第7周有进一步的升高(P<005)。SP免疫细胞化法检测各组EGF的蛋白表达情况与上述mRNA结果相平行。结论EGF、HGF随肝纤维化进程逐渐升高,IL10可抑制纤维化大鼠肝星状细胞EGF、HGF的表达,具有抗纤维化作用。 Aim To study the effect of IL-10 on liver fibrosis and on the expression of EGF and HGF of HSC of hepatic fibrosis rat.Methods Hepatic fibrosis was induced by CCl_4 administration. Sixty male Spraque-Dawly(SD)rats were randomly divided into three groups:normal control group(group N,8 rats),hepatic fibrosis model group(group C,28 rats)and IL-10 treated group(group I,24 rats). At the beginning of the 7 th and 11th week, rats in each group were routinely perfused with pronase E and type IV Collagnase through portal vein catheter and the suspension obtained from the digested liver was centrifuged with 11% Nycodenz density gradient to isolate HSC. RT-PCR was used to analyze mRNA from freshly isolated cells. Immunocytochemistry was performed to detect protein expression in cultured HSC.Results Rat hepatic fibrosis was developed with the increase of the injection frequency of CCl_4 and HSC were successfully isolated. Compared with group N,EGF and HGF mRNA increased in group C (P<0.01),and significantly decreased after treatment with IL-10 (P<0.01) . For EGF mRNA,it was higher in group I than group N;As to HGF,it was lower in group I than group N. EGF mRNA expression in group C increased at the 11 th week in contrast to the 7th week. Results by immunocytochemistry of EGF were paralleled with the above findings.Conclusion The expression of EGF and HGF mRNA increased in HSC with the development of rat hepatic fibrosis and decreased after treatment with IL-10. IL-10 plays an antifibrogenic activity by suppressing growth factor expression.
出处 《中国药理学通报》 CAS CSCD 北大核心 2005年第3期327-331,共5页 Chinese Pharmacological Bulletin
基金 福建省科技计划基金资助项目(No2003D05)
关键词 肝星状细胞 肝纤维化 白介素-10 表皮生长因子 肝细胞生长因子 hepatic fibrosis hepatic stellate cells interleukin-10 epithermal growth factor hepatocyte growth factor
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