罗格列酮对单侧输尿管梗阻大鼠肾间质纤维化的保护作用及其机制

Mechanism of rosiglitazone anti-fibrosis effect on unilateral ureteral obstruction rats

目的 :探讨罗格列酮 (RSG)对单侧输尿管梗阻 (UUO)大鼠肾间质纤维化的保护作用及其机制。方法 :将大鼠随机分成UUO组和UUO +RSG组 ,另设假手术组 (SHAM)为对照。用药组于术前 3d给予RSG 3 0mg·kg-1·d-1,ig ,直至术后 14d处死动物 ,对照组给予等量的灭菌去离子水同样处理。观察左侧肾脏病理学改变 ,比较肾间质基质含量和肾间质纤维化程度 ;以α 平滑肌肌动蛋白 (α SMA)的免疫组化结果观察肾小管上皮细胞转型情况。结果 :与UUO组相比 ,RSG +UUO组左侧肾脏的病理改变及肾间质纤维化程度明显减轻 (P <0 0 5 ) ,肾小管上皮细胞α SMA的表达显著减少 (P <0 0 5 ) ;而SHAM组对左侧肾脏病理学无显著影响。结论 :RSG对UUO所致的大鼠肾间质纤维化具有保护作用 ,其机制可能部分是通过减少肾小管上皮细胞向肌纤维细胞的转型 。

AIM: To observe the roles of rosiglitazone (RSG) in unilateral ureteral obstruction (UUO) rats renal interstitial fibrosis. METHODS: Animal were randomly divided into sham-operated(SHAM), UUO and UUO administration with RSG (UUO+RSG), respectively. RSG 30 mg·kg -1·d -1 or vehicle was administrated daily gavage 3 d before UUO and continued for 14 d after UUO. Compared the pathological change of left renal tissue by PAS staining. The renal cortical interstitial volume was determined on sections stained by Masson's trichrome method. Induction of interstitial myofibroblasts was assessed by immunohistochemical detection of α-smooth actin (α-SMA). A computer-aided manipulator was used for image analysis. RESULTS: RSG can effectively ameliorate UUO renal interstitial fibrosis index (P<0.05), reduce renal tubular epithelial cell α-SMA expression (P<0.05), which demonstrate an inhibitive effect on renal tubular epithelial cell transdifferentiation to myofibroblast. CONCLUSION: RSG has protective effects on UUO rats. The mechanism of these protective roles may partly with it reduced UUO rats renal tubular epithelial cell transdifferentiation to myofibroblast, therefore ameliorate UUO renal interstitial fibrosis.