鞣花酸对马兜铃酸I所致肾小管上皮细胞毒性的保护作用  

Ellagic acid protect against the cytotoxic effects of aristolochic acid I on human renal tubular epithelial cells

作　　者：舒广文[1] 雷霄 付千 阿尔斯拉·玉苏甫 孙慧 邓旭坤[1] SHU Guangwen;LEI Xiao;FU Qian;YUSUF Arslan;SUN Hui;DENG Xukun(School of Pharmaceutical Sciences&National Demonstration Center for Experimental Ethnopharmacology Education,South-Central Minzu University,Wuhan 430074,China)

机构地区：[1]中南民族大学药学院&民族药学国家级实验教学示范中心,武汉430074

出　　处：《中南民族大学学报（自然科学版）》2023年第4期462-468,共7页Journal of South-Central University for Nationalities：Natural Science Edition

基　　金：国家民委高等教育教学改革研究项目(21008);中央高校基本科研业务费专项资金资助项目(CDZ19007)。

摘　　要：探究了鞣花酸(ellagic acid,EA)对马兜铃酸I(aristolochic acids I,AAI)诱导的HK-2人肾小管上皮细胞毒性的保护作用和潜在机制.用噻唑蓝(MTT)比色法,乳酸脱氢酶(LDH)活性检测法评价了细胞活力;用Hoechst 33258荧光染色法和流式细胞分析法(FITC-Annexin V/PI双染)检测了细胞凋亡;用免疫印迹和实时荧光定量PCR检测了细胞内NF-κB和NLRP3通路相关因子的表达水平.结果显示:EA显著改善了AAI所致的HK-2细胞活力下降与凋亡增加的现象.进一步研究表明,AAI通过激活NF-κB上调HK-2细胞内NLRP3炎症小体组分编码基因的转录.EA则能明显阻断AAI对NF-κB/NLRP3通路的激活作用.综上所述,EA能明显缓解AAI诱导的HK-2细胞的毒性,其作用机制可能与阻断AAI对细胞内NF-κB/NLRP3级联的激活作用紧密相关.The protective activities of ellagic acid(EA)against the cytotoxic effects of aristolochic acid I(AAI)on human HK-2 renal tubular epithelial cells were explored,and the potential molecular mechanisms were dicucssed.Cell viability was detected by methyl thiazolyl tetrazolium(MTT)colorimetric assay and lactic acid dehydrogenase(LDH)activity assay.Hoechst 33258 fluorescent staining and flow cytometry analysis(FITC-Annexin V/PI double staining)performed to detect cell apoptosis.Levels of factors related with NF-κB and NLRP3 pathways were determined by immunoblotting and quantitative real-time PCR.The results revealed that AAI-induced decline of cell viability and apoptosis were considerably reduced by EA.Further studies revealed that AAI elevated the transcription of encoding genes of NLRP3 inflammasome components via potentiating NF-κB in HK-2 cells.Moreover,EA inhibited AAI-mediated activation of NF-κB/NLRP3 cascade.Collectively,EA dramatically alleviated AAI-induced cytotoxicity in HK-2 cells.Suppression of AAI-mediated activation of intracellular NF-κB/NLRP3 cascade is implicated in its renal protective effect.

关 键 词：马兜铃酸 鞣花酸 HK-2肾小管上皮细胞 NF-κB/NLRP3级联 

分 类 号：Q.26[生物学] R961.1[医药卫生—药理学]