大黄素通过调控ROS和NLRP3炎症体通路改善草酸钙结晶诱导的肾小管上皮细胞损伤  

Emodin protects against calcium oxalate crystal-induced renal tubular epithelial cell damage via ROS and NLRP3 inflammasome pathways

作　　者：高丙鹏 田静 靳银山 刘亚东[3] 于时良[3] 刘健男[3] GAO Bingpeng;TIAN Jing;JIN Yinshan;LIU Yadong;YU Shiliang;LIU Jiannan(Department of Urology,Bijie First Hospital,Bijie 551700;Qixingguan Chinese Medicine Hospital,Bijie 551700;Department of Urology,First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]毕节市第一人民医院泌尿外科,贵州毕节551700 [2]毕节市七星关区中医院,贵州毕节551700 [3]哈尔滨医科大学附属第一医院泌尿外科,黑龙江哈尔滨150001

出　　处：《现代泌尿外科杂志》2021年第6期525-528,540,共5页Journal of Modern Urology

基　　金：国家自然科学基金项目(No.81600543)。

摘　　要：目的研究大黄素是否能通过调控活性氧(ROS)及NLRP3炎症体通路抑制草酸钙结晶引起的肾小管上皮细胞氧化应激及炎症损伤。方法人肾皮质近曲小管上皮细胞培养后分别给予草酸钙结晶及大黄素干预。用细胞增殖与毒性试验检测细胞活性;蛋白印迹(Western blot)分析检测相关炎症蛋白的表达;流式细胞术检测ROS的表达;酶联免疫吸附试验(ELISA)检测细胞分泌炎症因子水平。结果细胞增殖与毒性试验显示大黄素可以缓解草酸钙晶体造成的细胞活性损伤。10μmol/L大黄素预处理后,流式细胞术显示大黄素显著降低草酸钙晶体引起的ROS升高,Western blot及ELISA试验表明大黄素可以显著抑制草酸钙晶体引起的相关炎症因子(NLRP3、ASC、Pro-caspase-1、Cleaved-caspase-1、IL-18、IL-1β)的表达与分泌。结论大黄素通过调控ROS及NLRP3炎症体通路抑制草酸钙结晶引起的肾小管上皮细胞损伤。Objective To investigate whether emodin can inhibit the calcium oxalate(CaOx)crystal-induced oxidative stress and inflammatory damage of renal tubular epithelial cells by regulating reactive oxygen species(ROS)and NLRP3 inflammasome pathways.Methods HK 2 cells were cocultured with CaOx crystals and emodin.Cell activity,expression of related inflammatory proteins,expression of ROS and levels of inflammatory factors were detected with CCK-8 kits,Western blotting,flow cytometry and enzyme-linked immunosorbent assay(ELISA),respectively.Results CCK-8 assays showed that emodin alleviated cell activity damage caused by CaOx crystals.After pretreatment with 10μmol/L emodin,flow cytometry showed emodin significantly reduced the ROS increase,and Western blotting and ELISA tests showed emodin significantly inhibited the expressions and secretion of related inflammatory factors,including NLRP3,ASC,Pro-caspase-1,Cleaved-caspase-1,IL-18 and IL-1β.Conclusion Emodin inhibits the CaOx crystal-induced renal tubular epithelial cell damage by regulating ROS and NLRP3 inflammasome pathways.

关 键 词：大黄素 草酸钙 肾结石 NLRP3炎症体 活性氧 炎症 

分 类 号：R692.4[医药卫生—泌尿科学]