SOCS3对四氯化碳诱导的小鼠肝纤维化进展和逆转的影响及机制研究  

Effect of SOCS3 on progress of liver fibrosis and reverse in mice induced by carbon tetrachloride and its mechanism

作　　者：夏家露 严醒 刘亚如[1] 黄成[1] 李俊[1] 

机构地区：[1]安徽医科大学药学院、安徽医科大学肝病研究所、安徽天然药物活性研究省级实验室,安徽省创新药物产业共性研究院,安徽合肥230032

出　　处：《中国药理学通报》2017年第9期1215-1221,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273526,81473268);安徽省教育厅重点基金项目(No KJ2016A364,KJ2016A365);安徽省自然科学基金面上项目(No21408085MKL31)

摘　　要：目的观察细胞因子信号传导抑制蛋白-3(suppressor of cytokine signaling3,SOCS3)对肝纤维化进展和逆转过程的影响。方法皮下注射四氯化碳(carbon tetrachloride,CCl4)建立C57BL/6小鼠肝纤维化模型,纤维化模型成功后正常饮食喂养1个月为纤维化逆转模型,以同体重、同性别的正常小鼠为对照组。分别在1、2、3、4、5、6、7、8周后处死小鼠,取肝组织,HE染色观察肝组织损伤情况,Masson染色观察胶原变化,免疫组织化学法观察Ⅰ型胶原(collagenⅠ,Colla-1)、α平滑肌肌动蛋白(αsmooth muscle actin,α-SMA)、转化生长因子β1(transforming growth factor beta1,TGF-β1)和SOCS3蛋白表达。体外用TGF-β1刺激HSC-T6细胞株形成纤维化体外模型,MDI培养基逆转纤维化过程,SOCS3过表达质粒作用于逆转过程,Western blot方法检测SOCS3、Colla-1、α-SMA、TGF-β1表达情况。结果 SOCS3和TGF-β1在小鼠纤维化模型中随着纤维化加重而表达增加,逆转过程中减少,过表达逆转过程,纤维化指标降低,有利于逆转的进行,TGF-β1表达也相应降低。结论SOCS3可能通过调控TGF-β1的表达参与肝脏纤维化的形成和逆转过程。Aim To observe the effects of cytokine signaling inhibition protein-3（ SOCS3） on the liver fibrosis progression and reverse. Methods C57BL/6 mouse model was established by subcutaneous injection of carbon tetrachloride（ CCl4）. After a successful model of fibrosis,one-month normal diet was given to induce the reverse fibrosis model,while normal mice of the same gender and weight were as control group. Mice were sacrificed at 1,2,3,4,5,6,7,8 weeks,respectively,then the liver tissue was harvested for the observation of its injury by hematoxylin and eosin（ HE）staining. Then Masson staining was applied for the detection of changes in collagen,and the immunohistochemistry（ IHC） for the observation of type Ⅰ Collagen（ Colla-1）,alpha smooth muscle actin（ α-SMA）,transforming growth factor beta 1（ TGF-β1） and SOCS3 protein expression. In vitro formation of fibrosis was induced by TGF-β1 stimulating HSC-T6 cell lines,which was then reversed by MDI medium,with co-incubation of HSC-T6 cells with plasmid in the process of the reverse. Western blot was employed to detect SOCS3,Colla-1,α-SMA,TGF-β1 expression. Results The expression of SOCS3 and TGF-β1 increased in mouse model of fibrosis with the worsening fibrosis process and decreased in the reverse process. Over-expression SOCS3 in the reverse process reduced the development of liver fibrosis; meanwhile,the expression of TGF-β1 was also reduced accordingly. Conclusion SOCS3 may influence the development of the liver fibrosis and its reverse via regulating the expression of TGF-β1.

关 键 词：SOCS3 肝脏纤维化 肝脏纤维化逆转 TGF-β1 HSC-T6 MDI 

分 类 号：R-332[医药卫生] R322.47