医学分子生物学杂志2024,Vol.21Issue(2):146-153,8.DOI:10.3870/j.issn.1672-8009.2024.02.009
白藜芦醇抑制肾纤维化减轻单侧输尿管梗阻诱导的肾损伤
Resveratrol Inhibits Renal Fibrosis and Reduces Kidney Damage Caused by Unilateral Ureteral Obstruction
摘要
Abstract
Objective To investigate the effect of resveratrol on renal fibrosis and kidney dam-age induced by unilateral ureteral obstruction and its related mechanism.Methods Sprague-dawley(SD)rats and NRK-49F fibroblasts were used as experimental subjects for in vivo study and in vitro validation.In vivo,TIF rat model was establish by surgery to induce the unilateral ureteral obstruc-tion in SD rats,and the rats were then randomly divided into 4 groups:sham operation + blank group,sham operation +resveratrol group,model +blank group and model +resveratrol group,12 rats in each group.In vitro:NRK-49F cells were treated with recombinant TGF-β1(5 ng/mL)or resveratrol(10 and 100 μmol/L)and randomly divided into 4 groups:control group,TGF-β1 group,TGF-β1 + resveratrol low-dose group and TGF-β + resveratrol high-dose group.Masson's staining was used to detect total collagen deposition in the kidney.Immunohistochemical staining was used to detect the expression of E-cadherin,GFAP and Ki67 in the tissues.Immunofluorescence staining was used to detect the expression of Ki67 in cells.Western blotting was used to detect the expression level of Vimentin,N-cadherin,Racl,c-Myc,Bcl-2,Cyclin D1,α-SMA,type Ⅰ col-lagen and type Ⅲ collagen,E-cadherin.Results Resveratrol could inhibit the excessive deposition of total collagen in kidneys of UUO rats,down-regulate α-SMA-positive myofibroblasts,reduce the expression of vimentin,type Ⅰ and type Ⅲ collagen,and inhibit the up-regulation of Rac1,GFAP and down-regulation of N-cadherin.Resveratrol could significantly reduce the ratio of Ki67-positive cells in UUO rats and inhibit the expression level of c-Myc,Bcl-2 and cyclin D1.Resveratrol inhibi-ted the activation of proliferation-related pathway Wnt/β-catenin.The in vitro experimentsshowed that resveratrol treatment could reduce the proliferation of fibroblasts and TECs,thereby inhibiting TGF-β1-mediated phenotypic transformation and ECM accumulation.Conclusion Resveratrol in-hibits the activity of Wnt/β-catenin pathway and the accumulation of myofibroblasts,and reduces renal tubulointerstitial fibrosis.关键词
慢性肾病/白藜芦醇/单侧输尿管梗阻/肾小管间质纤维化/细胞外基质/Wnt/β-catenin通路Key words
chronic kidney disease/resveratrol/unilateral ureteral obstruction/renal tubule interstitial fibrosis/extracellular matrix/Wnt/β-catenin pathway分类
医药卫生引用本文复制引用
詹宏义,宋亚玲,贺绍林,周杨洋..白藜芦醇抑制肾纤维化减轻单侧输尿管梗阻诱导的肾损伤[J].医学分子生物学杂志,2024,21(2):146-153,8.基金项目
重庆市大足区科技发展项目(No.DZKJ2023JSYJ-KWXM1031) This work was supported by a grant from the Chongqing Dazu District Science and Technology Development Project(No.DZKJ2023JSYJ-KWXM1031) (No.DZKJ2023JSYJ-KWXM1031)