二甲双胍通过抑制NF-κB/NLRP3通路改善草酸钙诱导人肾小管上皮细胞损伤研究  

Research on metformin inhibits the NF-κB/NLRP3 pathway to improve human renal tubular epithelial cell injury induced by calcium oxalate

作　　者：周吾溪 王海荣[1] 徐友胜 戚剑烽 陆顶进 ZHOU Wu-xi;WANG Hai-rong;XU You-sheng(Beihai People's Hospital,Department of Urinary surgery,Beihai 536000,China)

机构地区：[1]北海市人民医院泌尿外科,广西北海536000

出　　处：《中国处方药》2024年第1期18-22,共5页Journal of China Prescription Drug

基　　金：广西医科大学青年科学基金资助项目(GXMUYSF202138)。

摘　　要：目的研究二甲双胍(metformin,Met)通过抑制NF-κBNLRP3通路改善草酸钙(Calcium Oxalate,CaOx)诱导人肾小管上皮细胞(HK-2)损伤。方法分别随机将人肾小管上皮细胞分成对照组、实验组(CaOx+HK-2)、高浓度Met组(CaOx+HK-2+1.2 mM Met)、低浓度Met组(CaOx+HK-2+0.80 mM Met)、通路干预组(CaOx+HK-2+PDTC)五组。各组细胞培养24 h,采用酶联免疫吸附测定(Elisa)法检测细胞上清液中炎症因子(IL-6、IL-18、IL-1β),采用逆转录-聚合酶链反应(RT-PCR)法检测细胞中NF-κB、NLRP3、骨桥蛋白(OPN)mRNA。结果各组间细胞上清液IL-6、IL-18、IL-1β含量相比差异均有统计学意义(P均<0.05);各组间细胞中NF-κBmRNA表达量、NLRP3mRNA表达量、OPNmRNA表达量相比差异均有统计学意义(P均<0.05)。结论1.20 mmol/L或0.80 mmol/L Met可以通过抑制NF-κB/NLRP3通路调控下游的炎症相关蛋白及黏附蛋白表达,继而改善CaOx诱导人肾小管上皮细胞损伤及减少草酸钙肾结石形成。Objective To observe metformin inhibits the NF-κB/NLRP3 pathway to improve human renal tubular epithelial cell(HK-2)injury induced by calcium oxalate.Methods Human renal tubular epithelial cells were randomly divided into five groups:control group,experimental group(CaOx+HK-2),high concentration Met group(CaOx+HK-2+1.2 mM metformin),low concentration Met group(CaOx+HK-2+0.8 mM metformin)and pathway intervention group(CaOx+HK-2+PDTC).The cells in each group were cultured for 24 h.The inflammatory cytokines(IL-6,IL-18,IL-1β)in the cell supernatant were detected by Elisa,and the mRNA of NF-κB,NLRP3 and OPN in the cells were detected by RT-PCR.Results The differences of content of IL-6,IL-18,IL-1βbetween each group were significant(all P<0.05).The differences of relative expression levels of NF-κBmRNA,NLRP3mRNA,OPNmRNA between each group were significant(all P<0.05).Conclusion Metformin(1.20 or 0.80 mmol/L)inhibited the NF-κB/NLRP3 pathway to regulate the expression of downstream inflammation-related proteins and adhesion proteins,then improved calcium oxalate induced human renal tubular epithelial cell injury and reduced calcium oxalate kidney stone formation.

关 键 词：二甲双胍 草酸钙肾结石 人肾小管上皮细胞 NF-ΚB NLRP3 

分 类 号：R965[医药卫生—药理学]