葡萄糖与尿酸对肾小管上皮细胞与巨噬细胞共培养体系NLRP3炎性体的影响  

Effects of Glucose and Uric Acid on NLRP3 Inflammasome in A Coculture System of Human Renal Tubular Epithelial Cells and Macrophages

作　　者：肖木芳 冉建民 文罗娜 邱静娴 陈楚坪 刘岩[3] 谭荣韶[3] 覃丽英 XIAO Mufang;RAN Jianmin;WEN Luona(Medical Examination Center,Affiliated Xiaolan Hospital,Southern Medical University,Zhongshan,China,528400;不详)

机构地区：[1]南方医科大学附属小榄医院体检中心,中山528400 [2]暨南大学附属广州红十字会医院内分泌科,广州510220 [3]暨南大学附属广州红十字会医院临床病态营养研究所,广州510220

出　　处：《中国中西医结合肾病杂志》2023年第5期393-397,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：广东省协同创新与平台环境建设项目(No.2017B090904027)。

摘　　要：目的:观察不同浓度葡萄糖和尿酸对人肾小管上皮(HK-2)细胞及巨噬细胞共培养体系NLRP3炎性体的作用。方法:两种葡萄糖浓度和4种尿酸浓度交互分为8组,两种细胞在Transwell小室共培养72 h。检测HK-2细胞凋亡率、培养液中NLRP3、ASC、Caspase-1、IL-1β、IL-18含量及两种细胞上述因子的基因表达。结果:(1)HK-2细胞凋亡率随葡萄糖和尿酸浓度升高而升高;且两者有协同作用(P<0.05)。(2)上清液中,高葡萄糖浓度增加ASC、NLRP3、IL-1β的水平(P<0.05),而尿酸无明显影响。(3)HK-2细胞中除NLRP3外,其他因子基因表达水平随尿酸浓度升高而升高(均P<0.05);但葡萄糖无明显影响。(4)巨噬细胞中ASC、IL-1β、IL-18的基因表达水平在高葡萄糖浓度中升高(P<0.05);而尿酸无明显影响。结论:巨噬细胞和HK-2细胞NLRP3炎性体通路基因表达水平分别呈葡萄糖和尿酸浓度依赖性;IL-1β可能主要来自巨噬细胞;高糖及高尿酸协同诱导HK-2细胞凋亡。Objective:To investigate effects of glucose and uric acid on NLRP3 inflammasome in a coculture system including HK-2 cells and macrophages.Methods:Cells in Transwell system were cultivated for 72 h in glucose crossed with four escalated UA concentrations.Apoptotic rate of HK-2 cells were assayed;supernatant concentrations and gene expressions of NLRP3,ASC,Caspase-1,IL-1βand IL-18 were also measured.Results:(1)The apoptotic rate of HK-2 cells increased significantly along with the elevated glucose and UA;and the interaction between glucose and UA was also significant(P<0.05).(2)Supernatant concentrations of ASC、NLRP3,IL-1βwere significantly increased after stimulation with high glucose(all P<0.05),while not changed along with the elevated UA.(3)For HK-2 cells,except for NLRP3,the mRNA levels of ASC,IL-1β,IL-18 and Capase-1 showed coherently increased along with the elevated UA concentrations(all P<0.05),while high glucose concentration showed no significant effects.(4)For macrophages,mRNA levels of ASC,IL-1βand IL-18 showed coherently increased after high glucose stimulation(all P<0.05);all mRNA levels did not changed along with the increased UA concentrations.Conclusion:Genes expression of the NLRP3 inflammatory pathway showed glucose-dependent increase in macrophages but UA-dependent increase in tubular epithelia,respectively.Macrophages play a major role for the glucose-dependent increase of IL-1β;high concentrations of glucose and UA synergistically induced apoptosis in HK-2 cells.

关 键 词：尿酸 葡萄糖 肾小管上皮细胞 巨噬细胞 NLRP3炎性体 

分 类 号：R692.6[医药卫生—泌尿科学]