三七总皂苷对单侧输尿管梗阻大鼠肾组织BMP-7及TGF-β1/samds信号传导通路的影响

摘要

目的 观察三七总皂苷(PNS)对单侧输尿管梗阻(UUO)大鼠肾组织骨形成蛋白-7(BMP-7)及TGF-β1/Smads信号传导通路的影响.方法 将50只雄性Wistar大鼠随机分为5组:假手术组、模型组、肾康注射液组(对照组)、PNS低剂量组(低剂量组)、PNS高剂量组(高剂量组),每组10只,除假手术组,其余各组用UUO法建立肾间质纤维化动物模型,术前1 d起各组给予相应浓度和剂量的药物,术后第14天处死所有大鼠,检测大鼠血肌酐(Scr)和尿素氮(BUN)变化,梗阻侧肾组织行HE染色、PAS染色和Masson染色,观察肾组织病理变化并半定量计算肾小管损伤指数(TII),免疫组化法检测BMP-7、TGF-β1、Smad2、Smad7在肾组织的表达.结果 与模型组相比,PNS和肾康注射液能明显降低UUO大鼠术后14 d Scr、BUN(P＜0.05);对梗阻侧肾组织HE染色、PAS染色进行TII评分发现,2个试验组大鼠肾小管损伤指数显著低于模型组(P＜0.01);Masson染色观察发现,2个实验组大鼠肾小管间质病变明显轻于模型组;免疫组化法染色并对其灰度值测定发现,与模型组相比,2个试验组大鼠TGF-β1、Smad2在肾组织的表达下调(P＜0.01),BMP-7、Smad7在肾脏组织的表达上调(P＜0.01).结论 PNS可能通过干预BMP-7/Smads/TGF-β1信号转导通路抑制了TGF-β1信号的细胞内转导,而起到抗肾间质纤维化的作用.%Objective:To study the effects of Saponins of Panax Notoginseseng ( PNS )on BMP -7 and TGF - β, ,Smad2 and Smad7 expressions of renal interstitial fibrosis in Rats with unilateral ureteral obstruction( UUO ). Methods;50 male Wistar rats were divided randomly into five groups( n = 10 ); the sham operation group, the model group, Shenkang injection group ( control group), the low-dosage of PNS group ( low dosage group) and high dosage of PNS group ( high dosage group ). Except the rats in the sham operation group, the other rats were established renal interstitial fibrosis animal model by UUO. Medicine was given to each group according to the designed concentration and dosage from the day before the operation. The rats were killed on the fourtheenth day. Serum creatinine( Scr ),blood urea nitrogen( BUN ) were measured. Histological change in the obstructed kidney was examined by HE stain , PAS stain and Masson stain. The protein expression of BMP -7 、TGF - β11,Smad2 and Smad7 in obstructed kidney tissues were detected by ELISA respectively. Results;Compared with that in the model group, Scr, BUN and Til were significantly decreased by PNS in the 2 PNS groups. While Tubulointerstitial was improved by Masson stain. The protein expression of TGF - β1, Smad2 were down-regulated by PNS in the obstructed renal tissue of 2 PNS groups ,while The protein expression of BMP -7 .,Smad7 were down-regulated. Conclusion; The renal interstitial fibrosis may be inhibitted by PNS through TGF - βsmads signaling pathway was interferenced in the renal tissues of UUO rats.