三七总皂甙通过Smads信号通路减缓慢性肾衰竭大鼠肾间质纤维化进程的作用研究  

Panax Notoginseng Saponins Reduce Renal Interstitial Fibrosis in Chronic Renal Failure Rats Through Smads Pathway

作　　者：高洁[1] 刘益涛[1] 董华[1] 王雅宁[1] 常相帝 GAO Jie;LIU Yitao;DONG Hua;WANG Yaning;CHANG Xiangdi(Department of Nephrology,Affiliated Hospital of Binzhou Medical College,Binzhou 256603 Shandong,China)

机构地区：[1]滨州医学院附属医院肾内科,山东滨州256603

出　　处：《中药新药与临床药理》2021年第6期799-805,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：山东省医药卫生科技发展计划项目(2016WS0048)。

摘　　要：目的探讨三七总皂甙(panax notoginseng saponins,PNS)通过Smads信号通路减缓慢性肾衰竭(chronic renal failure,CRF)大鼠肾间质纤维化进程的作用。方法 60只大鼠随机留取10只设为假手术组,其余50只采用5/6肾切除术复制CRF模型,将建模成功的44只大鼠随机分为慢性肾衰竭组、尿毒清组、三七总皂甙低剂量组(LPNS组)、三七总皂甙高剂量组(HPNS组),每组11只。尿毒清组灌胃2.2 g·kg^(-1)的尿毒清溶液,三七总皂甙低剂量组和三七总皂甙高剂量组灌胃25、100 mg·kg^(-1)的三七总皂甙溶液,假手术组和慢性肾衰竭组灌胃等量生理盐水溶液,连续4周。干预结束后,检测各组肾功能指标:血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白,HE和Masson染色观察残余肾组织病理学改变及肾组织纤维化面积占比,RT-qPCR和Western Blot法检测残余肾组织中转化生长因子β1(TGF-β1)、Smad2/3、Smad6 mRNA表达量及TGF-β1、Smad2/3、p-Smad2/3、Smad6蛋白表达量。结果与慢性肾衰竭组比较,尿毒清组、三七总皂甙低剂量组、三七总皂甙高剂量组血肌酐、尿素氮、24 h尿蛋白水平均降低,三七总皂甙高剂量组低于三七总皂甙低剂量组和尿毒清组(均P<0.05)。HE染色显示,慢性肾衰竭组可见肾小球、肾小管明显病变,肾间质纤维化增生,大量炎性细胞浸润;尿毒清组、三七总皂甙低剂量组、三七总皂甙高剂量组上述病变减轻,其中三七总皂甙高剂量组病变最轻。与慢性肾衰竭组比较,尿毒清组、三七总皂甙低剂量组、三七总皂甙高剂量组肾组织纤维化面积占比、TGF-β1 mRNA相对表达量及TGF-β1、p-Smad2/3蛋白相对表达量均降低,三七总皂甙高剂量组低于三七总皂甙低剂量组和尿毒清组(均P<0.05)。与慢性肾衰竭组比较,尿毒清组、三七总皂甙低剂量组、三七总皂甙高剂量组Smad6 mRNA和蛋白相对表达量升高,三七总皂甙高剂量组高于三七总皂甙低剂量组和尿毒�Objective To investigate the effect of panax notoginseng saponins(PNS) on the process of renal interstitial fibrosis in chronic renal failure(CRF) rats through Smads signaling pathway.Methods Ten of 60 rats were randomly selected as sham operation group,and the remaining 50 rats were performed 5/6 nephrectomy to prepare CRF model.44 rats were successfully modeled and randomly divided into CRF group,Niaoduqing group,and PNS low-dose group(LPNS group),PNS high-dose group(HPNS group),each with 11 rats.Niaoduqing group was given intragastrically with 2.2 g·kg^(-1) Niaoduqing solution,LPNS group and HPNS group were given 25,100 mg·kg^(-1)PNS solution,sham operation group and CRF group were given the same amount of physiological saline solution for 4 consecutive weeks.After intervention,the renal function indexes of each group,including blood creatinine(Scr),urea nitrogen(BUN)and 24 h urine protein were detected.The pathological changes of residual renal tissue and the area ratio of renal tissue fibrosis were detected by HE and Masson staining.Transforming growth factor β1(TGF-β1),Smad2/3,Smad6 m RNA expression and TGF-β1,Smad2/3,p-Smad2/3,Smad6 protein expression in residual kidney tissue were detected by RT-q PCR and Western blot.Results Compared with the CRF group,the Scr,BUN,and 24-hour urine protein levels in the Niaoduqing group,LPNS group and HPNS group were low.The levels mentioned above in the HPNS group were lower than in the LPNS group and the Niaoduqing group(P<0.05).HE staining showed that there were obvious glomerular and renal tubule lesions,renal interstitial fibrosis and proliferation,and a large number of inflammatory cell infiltration in the CRF group.The abovementioned lesions in the Niaoduqing group,LPNS group,and HPNS group were alleviated,and the lightest lesions were found in the HPNS group.Compared with the CRF group,the area ratio of renal tissue fibrosis,the relative expression of TGF-β1 m RNA,TGF-β1 and p-Smad2/3 protein in the Niaoduqing group,LPNS group and HPNS group were low,and t

关 键 词：慢性肾衰竭 肾间质纤维化 三七总皂甙 SMADS信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]