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。
Research on metformin inhibits the NF-κB/NLRP3 pathway to improve human renal tubular epithelial cell injury induced by calcium oxalate
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-1β between 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.
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