尿石素A对转化生长因子-β1诱导的人近端肾小管上皮细胞纤维化的影响  

Effect of urolithin A on HK-2 fibrosis induced by transforming growth factor-β1

作　　者：李佳婷 李佳 李云龙 韩林 王敏[1] LI Jiating;LI Jia;LI Yunlong;HAN Lin;WANG Min(College of Food Science and Engineering,Northwest A&F University,Yangling 712100;Institute of Functional Food of Shanxi,Shanxi Agricultural University,Taiyuan 030031)

机构地区：[1]西北农林科技大学食品科学与工程学院,杨陵712100 [2]山西农业大学山西功能食品研究所,太原030031

出　　处：《中国食品添加剂》2023年第5期57-69,共13页China Food Additives

基　　金：国家自然科学基金青年科学基金项目(32001701);中西部药食兼用食物资源功能性物质研究及产业化(TG20220288);国家现代农业产业技术体系(CARS-08-E2-1)。

摘　　要：为探究尿石素A(urolithin A,UA)对人近端肾小管上皮细胞(HK-2)纤维化的干预效果和潜在作用机制,本研究建立转化生长因子-β1(transforming growth factor-β1,TGF-β1)诱导的HK-2纤维化模型,考察对照组、TGF-β1模型组(4 ng/mL处理48 h)、UA低浓度组(5μg/mL UA+4 ng/mLTGF-β1)、UA高浓度组(10μg/mL UA+4 ng/mLTGF-β1)对HK-2细胞的影响。试验结果表明:UA干预能改善TGF-β1引起的HK-2形态变化并显著降低细胞纺锤体指数(P<0.01);降低纤维化标物Col I、Col III、Vimentin、Snail和Slug和炎症标志物IL-1β、IL-6、MCP-1、NLRP3的表达(P<0.01);下调MAPK和TGF-β1/Smads信号通路相关蛋白的相对表达(P<0.01)。上述研究表明UA能减轻TGF-β1诱导的HK-2细胞纤维化,其作用的机制可能是通过下调MAPK和TGF-β1/Smads信号通路来实现的。本研究能为开发天然活性成分UA用于延缓肾纤维化提供新方法。In order to explore the intervention effect and potential mechanism of urolithin A(UA)on human proximal renal tubular epithelial cells(HK-2)fibrosis,transforming growth factor-β1(TGF-β1)-induced fibrosis model of HK-2 was established.The effect of different treatments on HK-2 fibrosis in control group,TGF-β1 model group(treated with 4 ng/mL for 48 h),low concentration of UA group(5μg/mL UA+4 ng/mLTGF-β1)and high concentration of UA group(10μg/mL UA+4 ng/mLTGF-β1)were investigated.The results showed that UA could improve morphological changes of HK-2 cells induced by TGF-β1,and significantly reduce the spindle index(P<0.01).The expressions of fibrosis markers Col I,Col III,Vimentin,Snail and Slug and inflammatory markers IL-1β,IL-6,MCP-1 and NLRP3 were decreased(P<0.01).UA could also down-regulate relative expression of MAPK and TGF-β1/Smads signaling pathway related proteins(P<0.01).The above studies suggested that UA could reduce the fibrosis of HK-2 cell induced by TGF-β1,which might be achieved through down-regulating MAPK and TGF-β1/Smads signaling pathways.This study provides a new method for the development of UA as a natural active ingredient to delay renal fibrosis.

关 键 词：尿石素A 纤维化 转化生长因子-Β1 HK-2 MAPK信号通路 

分 类 号：TS202.1[轻工技术与工程—食品科学] TS255.1[轻工技术与工程—食品科学与工程]