中国中医药信息杂志2024,Vol.31Issue(5):85-91,7.DOI:10.19879/j.cnki.1005-5304.202310018
基于Wnt/β-catenin/TRPC6/CaN通路探讨淫羊藿苷对激素抵抗性肾病综合征大鼠泼尼松抵抗的作用机制
Discussion on the Mechanism of Icariin in Improving Prednisone Resistance in Rats with Steroid-Resistant Nephrotic Syndrome Based on Wnt/β-catenin/TRPC6/CaN Pathway
摘要
Abstract
Objective To observe the improving effects of icariin on the improvement of prednisone resistance in steroid resistant nephrotic syndrome(SRNS)rats and its effects on the Wnt/β-catenin/TRPC6/CaN pathway.Methods Totally 50 SD rats were divided into blank group,model group,prednisone group(6.3 mg/kg),icariin group(50 mg/kg)and combination group,with 10 rats in each group.Twice tail vein injections of adriamycin were used to establish a SRNS rat model,and corresponding interventions were given for 6 weeks.General condition of rats was observed,24-hour urinary protein quantification(24 h-UTP),urine 17-hydroxycorticosteroids(17-OHCS),and serum biochemical indicators were detected,renal tissue pathological morphology and ultrastructure were observed by Masson staining,RT-PCR and Western blot were used to detect Wnt/β-catenin/TRPC6/CaN pathway related genes and protein expressions in renal tissue.Results Compared with the blank group,the body mass,feed intake and water intake of rats in the model group significantly decreased,24 h-UTP increased,urine 17-OHCS content decreased(P<0.01),the contents of serum creatinine(SCr),blood urea nitrogen(BUN),total cholesterol(TC)and triglycerides(TG)inserum increased(P<0.01),while the contents of total protein(TP)and albumin(ALB)decreased(P<0.05,P<0.01);glomerular enlargement,thickening of basement membrane,thickening of balloon wall with fibrosis,vacuolar degeneration of podocytes,and deposition of a large amount of collagen fibers appeared,collagen volume fraction(CVF)increased(P<0.01);Wnt,β-catenin,TRPC6,CaM,CaN and NFAT1 mRNA and protein expressions significantly increased(P<0.01),while the mRNA and protein expressions of F-actin and MYH9 were significantly reduced(P<0.01).Compared with the model group,rats in the combination group showed a significant increase in body mass and water intake,a decrease in 24 h-UTP,and an increase in urine 17-OHCS content(P<0.01);the contents of SCr,BUN and TG decreased(P<0.01);the degree of renal tissue fibrosis was reduced,CVF was reduced(P<0.01),foot process fusion phenomenon was significantly improved,and podocyte structure tends to be normal;Wnt,β-catenin,TRPC6,CaM,CaN and NFAT1 mRNA and protein expressions were significantly decreased,while the mRNA and protein expressions of F-actin and MYH9 significantly increased(P<0.01,P<0.05).Conclusion Icariin may inhibit Wnt/β-catenin/TRPC6/CaN pathway to upregulate the expression of skeleton proteins F-actin,MYH9,thereby protecting podocyte structure,slowing podocyte damage,and improving prednisone resistance in SRNS rats.关键词
激素抵抗性肾病综合征/淫羊藿苷/足细胞/阿霉素肾病/Wnt/β-catenin/TRPC6/CaN通路/大鼠Key words
steroid resistant nephrotic syndrome/icariin/podocyte/adriamycin nephropathy/Wnt/β-catenin/TRPC6/CaN pathway/rats分类
医药卫生引用本文复制引用
白俊嫄,戴恩来,蒲晓薇,张云霞..基于Wnt/β-catenin/TRPC6/CaN通路探讨淫羊藿苷对激素抵抗性肾病综合征大鼠泼尼松抵抗的作用机制[J].中国中医药信息杂志,2024,31(5):85-91,7.基金项目
国家自然科学基金(82160852) (82160852)