保元排毒丸对单侧输尿管梗阻大鼠肾小管上皮细胞转分化的影响

Effect of Baoyuan Paidu Pill on Transdifferentiation Of Renal Tubular Epithelial Cells in Rats With Unilateral Ureteral Obstruction

观察保元排毒丸对单侧输尿管梗阻(unilateral ureteral obstruction UUO)模型大鼠肾小管上皮细胞转分化的影响。方法:48只SD大鼠按随机数字表法分为假手术组、UUO组、厄贝沙坦组、保元排毒丸低、中、高剂量组各8只,假手术组只分离输尿管不结扎,其余均制备右侧UUO肾纤维化模型,造模第2天开始给予相应的药物灌胃,灌胃14 d。于末次灌胃后收集24 h尿液,眼眶采血,取右侧肾测24 h尿蛋白定量、血肌酐、尿素氮;HE和Masson染色观察肾脏病理改变,分别用免疫印迹和免疫组化测法测肾组织E-cadherin、а-SMA表达。结果:UUO组24 h尿蛋白定量、血肌酐、尿素氮均高于其他各组,肾小管、间质病变及纤维化重于其他各组,а-SMA表达最强, E-cadherin表达最弱。保元排毒丸低、中、高剂量组和厄贝沙坦组24 h尿蛋白定量、血肌酐、尿素氮均低于UUO组,肾小管、间质病变及纤维化程度轻于UUO组,а-SMA表达明显少于UUO组,E-cadherin表达高于UUO组。结论:保元排毒丸有改善肾脏纤维化的作用,其机理可能与调控肾小管上皮细胞转分化有关。

Objective： To investigate the effect of Baoyuan Paidu Capsules on epithelial mesenchymal transition in unilateral ureteral obstruction（UUO） rats. Methods： Forty-eight male Sprague Dawley rats were randomly divided into six groups： sham-operation group, UUO group, irbesatan group, high-, mid-, low-dose Baoyuan Paidu Capsules groups, 8 in each group. A rat model of renal fibrosis was prepared by unilateral ureteral obstruction.The 6 groups of rats were treated with corresponding drugs for 14 days, once a day. Then 24 h urine was collected and 24 h urinary protein（24 h UP） was detected.Serum blood urea nitrogen（BUN） and serum creatinine（Scr） were also tested. The right surgery renal tissue were collected for pathological examinations. The pathological changes of the obstruction renal tissue were examined by Hematoxylin and eosin staining（HE） and Masson staining. The protein expression of E-cadherin, a-smooth musle actin were detected by Western blot method and immunohistochemical staining respectively. Results Compared with the sham-operation group, 24 h UP, BUN and Scr was significantly increased in UUO group and other groups. renal tubular-interstitial index was significantly increased in UUO group and other groups. Compared with UUO group, renal tubular-interstitial index was significantly reduced in high-, mid-, low-dose Baoyuan Paidu Capsules groups and irbesatan group. Compared with those of UUO group, the protein expression of a-SMA was decreased significantly in all other groups, the protein expression of E-cadherin was increased obviously in high-, mid-, low-dose Baoyuan Paidu Capsules groups and irbesatan group. Conslution： Baoyuan Paidu Capsules can inhibit the renal tubulointerstitial fibrosis in UUO mice model probably by regulating epithelial mesenchymal transition.