实用肝脏病杂志 ›› 2015, Vol. 18 ›› Issue (1): 67-70.doi: 10.3969/j.issn.1672-5069.2015.01.017

• 实验性肝炎 • 上一篇    下一篇

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

李紫琼, 木尼拉, 高峰   

  1. 830000 乌鲁木齐市 新疆维吾尔自治区人民医院消化内科
  • 收稿日期:2014-05-16 出版日期:2015-12-17 发布日期:2015-12-17
  • 作者简介:李紫琼,男,37岁,医学硕士,主治医师。主要从事肝纤维化研究。E-mail:liazi2006@126.com

Inhibiting effects of antisense transforming growth factor β type I receptor and antisense TIMP-1 on experimental hepatic fibrosis in rats

Li Ziqiong, Mu Nila, Gao Feng   

  1. Department of Gastroenterology,People's Hospital,Xinjiang Uygur Autonomous Region,Urumchi 830000,Xin Jiang Uygur Autonomous Region,China
  • Received:2014-05-16 Online:2015-12-17 Published:2015-12-17

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