罗格列酮联合替米沙坦对单侧输尿管梗阻大鼠慢性肾纤维化的改善作用

Effects of rosiglitazone and telmisartan on of with chronic renal fibrosis after unilateral ureteral obstruction

关键词:  肾小管间质纤维化  罗格列酮  替米沙坦  基质金属蛋白酶-9  组织金属蛋白酶抑制物-1  转化生长因子-β1

Key words:  renal tubulointerstitial fibrosis  rosiglitazone  telmisartan  matrix metalloproteinase-9  tissue inhibitor of metalloproteinase-1  transforming growth factor-β1

摘要:

［目的］观察罗格列酮、替米沙坦单用及联合使用对单侧输尿管梗阻（UUO）大鼠肾脏纤维化的作用。［方法］大鼠随机分成5组，即假手术组、模型组、罗格列酮干预组、替米沙坦干预组、联合用药组。术后14 d处死，RT-PCR方法检测肾皮质TGF-β1及TIMP–1 mRNA的表达，Western blotting方法检测肾皮质中MMP-9蛋白的表达。［结果］罗格列酮、替米沙坦单用都可减轻UUO模型大鼠肾脏TGF-β₁和TIMP-1高表达；二者联合应用时，肾组织TGF-β₁和TIMP-1表达下降更有显著性意义（P<0.05）。罗格列酮、替米沙坦单用或联合应用对UUO模型大鼠肾组织MMP-9表达无明显影响（P>0.05）。［结论］罗格列酮、替米沙坦均可下调TGF-β₁的表达，纠正MMP-9/TIMP-l的失衡。

Abstract:

［Objective］To observe the effects of the combination of Rosiglitazone and Telmisartan on rats with chronic renal fibrosis in the unilateral ureteral obstrution(UUO) rats. ［Methods］Rats were randomly divided into five groups as described below: sham-operated group for control,unilateral ureteral obstruction group, Rosiglitazone treatment group, Telmisartan treatment group, combined treatment group. All the rats were killed at the 14th day after operation. RT-PCR,Western blotting were performed to examine the expression of TGF-β₁,TIMP-1 and MMP-9 in the obstructed kidney. ［Results］Treatment with RGZ or TEL could downregulate the expression of TGF-β₁ and TIMP-1. The combination of RGZ and TEL could decrease significantly the expression of TGF-β₁ and TIMP-1, compared with that in the single treatment of RGZ or TEL (P<0.05). There was no significant difference among groups in the expression of MMP-9(P>0.05). ［Conclusion］Rosiglitazone and Telmisartan can delay the progression of renal tubulointerstitial fibrosis, through down regulating the expression of TGF-β1 and ameliorating the imbalance of MMP-9/TIMP-1. Combination treatment of Rosiglitazone and Telmisartan showed better protective effect than single treatment.