反义I型转化生长因子β受体和反义TIMP-1联合作用对大鼠肝纤维化的抑制作用

doi:10.3969/j.issn.1672-5069.2015.01.017

摘要/Abstract

摘要： 目的观察转化生长因子βI型受体（TβRI）反义RNA联合TIMP-1反义RNA对实验性肝纤维化的影响。方法构建TβRI和TIMP-1反义RNA真核细胞表达质粒,共同导入实验性肝纤维化大鼠体内;应用免疫印记技术检测实验大鼠肝组织TIMP-1、TβRI和MMP-13蛋白表达水平。结果正常对照组、反义TβRI组、反义TIMP-1组、联合治疗组、空质粒组和模型组动物肝组织TIMP-1蛋白相对表达量分别为（23.6±2.8）、（57.96±3.8）、（62.3±2.8）、（34.2±2.8）、（279.2±29.8）和（287.3±23.7）,TβRI蛋白的相对表达量分别为（56.2±2.7）、（70.5.±1.8）、（77.0±1.7）、（60.6±2.2）、（232.0±19.4）和（241.0±18.3）,MMP-13蛋白相对表达量分别为（17.84±2.3）、（36.2±3.7）、（41.3±2.4）、（28.6±2.0）,（127.3±1.2）和（118.5±2.5）,与正常对照组及空质粒组比,反义TβRI组、联合治疗组和反义TIMP-1组TβRI、TIMP-1和MMP-13蛋白表达明显减少(P<0.05),但空质粒组与模型组比无显著性差异。结论 TβRI和TIMP-1反义RNA能有效抑制TβRI、TIMP-1和MMP-13蛋白表达,两者联合应用可产生叠加效应。

关键词: 肝纤维化, 反义RNA, 质粒, 转化生长因子β, 基质蛋白酶组织抑制因子

Abstract: Objective To observe the effects of transforming growth factor β type I receptor （TβRI） antisense RNA and tissue inhibitor of metalloproteinase 1（TIMP-1） antisense RNA on experimental liver fibrosis in rats. Methods TβRI and TIMP-1 antisense RNA eukaryotic expression plasmids were constructed and transfected into experimental rats with hepatic fibrosis. The impacts of TβRI and TIMP-1 antisense RNA on TIMP-1,TβRI and MMP-13 expression were detected by Western blot. Results The relative expressions of TIMP-1 protein in normal control group, antisense TβRI group, antisense TIMP-1 group, combinational group, plasmid group and model group were（23.6±2.8）,（57.96±3.8）,（62.3±2.8）,（34.2±2.8）,（279.2±29.8）and（287.3±23.7）,respectively;the relative expressions of TβRI in each groups were（56.2±2.7）,（70.5.±1.8）,（77.0±1.7）,（60.6±2.2）,（232.0±19.4） and（241.0±18.3）,respectively;and the relative expressions of MMP-13 were （17.84±2.3）,（36.2±3.7）,（41.3±2.4）,（28.6±2.0）,（127.3±1.2）and（118.5±2.5）,respectively. The relative expressions of TβRI,TIMP-1 and MMP-13 in antisense TβRI group, antisense TIMP-1 group and combinational group were significantly decreased compared with normal control group and plasmid group（P<0.05）,while there was no significantly differences between plasmid and model group. Conclusions Antisense TβRI RNA and antisense TIMP-1 RNA can both inhibit the expressions of TβRI,TIMP-1 and MMP-13 protein effectively,and their combination can improve the inhibiting effects.

Key words: Liver fibrosis, Antisense RNA, Plasmids, Transforming growth factor β, receptor, Tissue inhibitor of matrix metalloproteinases

李紫琼, 木尼拉, 高峰. 反义I型转化生长因子β受体和反义TIMP-1联合作用对大鼠肝纤维化的抑制作用[J]. 实用肝脏病杂志, 2015, 18(1): 67-70.

Li Ziqiong, Mu Nila, Gao Feng. Inhibiting effects of antisense transforming growth factor β type I receptor and antisense TIMP-1 on experimental hepatic fibrosis in rats[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(1): 67-70.

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