转化生长因子βⅠ型受体对组织纤维化形成及发展的影响  

Roles of TGFβR-Ⅰ in pathogenesis and development of tissue-fibrosis

作　　者：黄维亮[1] 苏先狮 陈放知[3] 万新星[1] 林蓉蓉[1] 谭博[1] 陈汉春[1] 

机构地区：[1]中南大学生物科学与技术学院生物化学系,长沙410013 [2]国狮基因研究所,长沙410011 [3]中南大学湘雅二医院泌尿外科,长沙410011

出　　处：《临床与实验病理学杂志》2010年第6期728-732,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(30371660);中华医学基金会基金(CMB99-698)

摘　　要：目的探讨转化生长因子βⅠ型受体(TGFβR-Ⅰ)对组织纤维化的形成及发展的影响。方法采用RNA干扰技术阻断人成纤维细胞系HFL-Ⅰ细胞的TGFβR-Ⅰ表达,Western blot法检测RNA干扰前后TGFβR-Ⅰ的表达水平,MTT法分析干扰前后的细胞生长状态,采用动物模型结合HE染色观察RNA干扰阻断TGFβR-Ⅰ表达前后的中毒性肝纤维化模型大鼠的肝脏病理学变化。结果特异性TGFβR-Ⅰ干扰RNA能有效抑制TGFβR-Ⅰ蛋白质合成和成纤维细胞株HFL-Ⅰ细胞的生长,正常鼠肝组织处于纤维化S0期,中毒性肝纤维化模型鼠肝组织处于纤维化S2期,特异性TGFβR-Ⅰ干扰RNA治疗组模型鼠肝组织则呈现纤维化S1期特征。结论抑制TGFβR-Ⅰ的表达可明显减轻中毒性肝纤维化模型大鼠的肝纤维化程度,对进一步优化肝纤维化的预防和治疗策略具有重要意义。Purpose To investigate the roles of transforming growth factor β receptorⅠ（TGFβR-Ⅰ）in the pathogenesis and development of tissue-fibrosis.Methods TGFβR-Ⅰ expression and cell growth of human fibroblast cell line HFL-Ⅰ cells were detected by Western blot and MTT assaying,respectively,before and after blocking TGFβR-I by employing RNA interference.The pathological changes of liver tissue of the rat models with toxic liver fibrosis were analyzed by hematoxylin-eosin staining before and after RNA interference to TGFβR-Ⅰ.Results TGFβR-Ⅰ biosynthesis and growth of HFL-I cells were significantly inhibited by the specific RNA interference to TGFβR-Ⅰ.The fibrosis features of S0 phase and S2 phase were seen in liver tissue from normal rats and the toxic liver fibrosis rats,respectively.However,the liver tissue from the rat models of toxic liver fibrosis after inhibiting TGFβR-Ⅰ expression by the specific RNA interference showed S1 phase of fibrosis.Conclusion The results show that inhibition of TGFβR-Ⅰ expression can reduce the level of liver fibrosis,which is significant for further optimizing the strategies on prevention and treatment of liver fibrosis.

关 键 词：转化生长因子βⅠ型 受体 纤维化 RNA干扰 

分 类 号：R575.2[医药卫生—消化系统]