莪术对单侧输尿管梗阻大鼠肾间质纤维化的影响

Effect of Curcuma Phaeocaulis Valeton on Renal Interstitial Fibrosis After Unilateral Ureteral Obstruction in Rats

目的探讨中药莪术对大鼠单侧输尿管梗阻动物模型(UUO)的影响及其可能机制。方法利用单侧输尿管梗阻的方法(UUO)建立大鼠肾间质纤维化的动物模型,并用中药莪术对其治疗,设为中药治疗组,以氯沙坦为西药对照组,采用免疫组化和原位杂交方法观察细胞外基质IV型胶元、α-SMA和TGF-β、NF-Kb、PAI-1的表达。应用医学病理图像分析系统对阳性面积进行统计学分析。结果动物实验莪术治疗组与模型组比较,免疫组化、原位杂交各检测指标统计学上有显著差异(P<0.05);莪术组TGF-β、NF-Kb、α-SMA、COL-Ⅳ、PAI-1mRNA表达明显低于模型组,各项检测结果也有显著差异(P<0.05)。莪术组肾间质原位杂交检测阳性面积表达明显低于模型组,有显著差异。结论莪术可能通过抑制与纤维化关系最密切的细胞因子如TGFβ1,核因子NF-Kb来抑制成纤维细胞活性,阻止MyoFb的出现,以及通过下调PAI-1来调节纤溶系统平衡,抑制细胞外基质合成,促进其降解等机制延缓肾间质纤维化。

Objective To explore the therapeutic efficacy and the mechanism of curcuma phaeocaulis valeton in rats by the unilaterall ureteral obstruction （UUO）. Methods Rat renal interstitial fibrosis model was produced in rats by the unilateral UUO. Curcuma phaeoeaulis valeton was used to treat the renal interstitial fibrosis. Transforming growth factor-β, nuclear factor-kappa B, PAl-1,α-SMA （a-smooth muscle actin） and collagens IV of renal extracellular matrix were determined immunohistochemically and in suit hybridize method. Pathology image analysis was performed to detect the positive expression. Result In comparison with the model group, parameters of col-Ⅳ, α-SMA TGF-β, NF-Kb and PAI-1mRNA in curcuma phaeoeaulis valeton treated group were obviously different. In addition, eurcuma phaeocaulis valeton could significantly decrease PAI-1 expression in the influenced tissue in suit hybridize （P〈 0.05）. Condusion Curcuma phaeocaulis valeton may play a prptective role to the kidney by inhibiting the over-expression of TGF-β, NF-Kb, PAl-1 and α-SMA in rats renal tubulointerstitium and decreasing the deposition of renal extracellular matrix（col-Ⅳ）, so it can reduce obviously the extent of renal interstitial fibrosis.