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法舒地尔对腹膜透析大鼠腹膜间皮细胞转分化的影响 被引量：5

Effect of fasudil on peritoneal mesothelium EMT in a rat model of peritoneal dialysis
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摘要 目的:观察Rho激酶(Rho-kinase)抑制剂法舒地尔对腹膜透析大鼠腹膜间皮细胞转分化的影响。方法:通过每日腹腔注射4.25%腹膜透析液建立腹膜透析大鼠模型。大鼠随机分为4组:正常对照组;腹膜透析模型组;法舒地尔5mg组;法舒地尔10mg组。4周后杀检大鼠,取脏层腹膜组织,分别用RT-PCR、Western杂交或免疫荧光方法检测转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)的表达,同时用Western杂交检测Rho-kinase活性。结果:法舒地尔呈剂量依赖模式显著抑制Rho-kinase活性。与正常组比较,腹膜透析模型组TGF-β1蛋白及mRNA表达显著上调,转分化指标α-SMA蛋白及mRNA表达明显上调(P<0.01),E-cadherin蛋白及mRNA显著下调(P<0.01),腹膜超滤量显著降低。法舒地尔干预后,TGF-β1蛋白及mRNA表达呈剂量依赖模式下调,α-SMA蛋白及mRNA表达呈剂量依赖模式下调,E-cadherin蛋白及mRNA表达呈剂量依赖模式上调,腹膜超滤量显著改善。结论:Rho-kinase激活在腹膜透析大鼠腹膜间皮细胞转分化中起重要作用。法舒地尔可通过抑制TGF-β1信号通路,阻止腹膜间皮细胞转分化,从而改善腹膜透析大鼠模型腹膜结构和功能。 Objective： To investigate whether Rho-kinase inhibition has a therapeutic role on the peritoneal mesothelium EMT in a rat model of peritoneal dialysis. Methodology： A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4. 25% Dianeal. Twenty four SD rats were divided into four groups：N Group is normal control group （n =6） ,PD Group is peritoneal dialysis group （n =6） ,Fas 5 mg （n =6） and Fas 10 mg group （n =6） was daily received respectively intraperitoneal injection of 4.25% Dianeal and 5 mg/kg or 10 mg/kg fasudil. Immunofluorescence,Western blot and RT-PCR were used to detect the expression of TGF-β1, a-SMA and E-cadherin in each group. The activity of Rho-kinase was determined by western immunoblotting. Results： Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil in a dose-dependent manner. Compared with normal group, the expressions of TGF-β1 and a-SMA in PD group were significantly increased, and the expression of E-cadherin was also markedly decreased. Compared with PD group,the mRNA and protein expressions of TGF-β1 and a-SMA were significantly downregulated in fasudil treatment groups in a dose-dependent manner, while the expression of E-cadherin was markedly upregulated in fasudil treatment groups in a dose-dependent manner. Conclusion：Rho-kinase activation play an important role in peritoneal mesothehum EMT in peritoneal dialysis rats, and the inhibition of Rhu-kinase by fasudil can significantly inhibit peritoneal mesothelium EMT and improve peritoneal structure and function.
作者 彭卫生 周巧玲 唐荣 肖舟
机构地区 中南大学湘雅医院肾脏内科长沙
出处 《肾脏病与透析肾移植杂志》 CAS CSCD 北大核心 2013年第2期134-138,157,共6页 Chinese Journal of Nephrology,Dialysis & Transplantation
关键词 腹膜透析 法舒地尔 腹膜间皮细胞转分化 peritoneal dialysis fasudil eprthelial-messenchymal transtition
分类号 R692.5 [医药卫生—泌尿科学]
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参考文献16

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同被引文献45

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引证文献5

二级引证文献11

肾脏病与透析肾移植杂志
2013年 第2期

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