兰州大学学报（医学版）2023，Vol.49Issue(10)：26-31,6.DOI:10.13885/j.issn.1000-2812.2023.10.004
重金属六价铬暴露后早衰肝细胞分泌表型中炎性成分的作用研究
Regulation and role of inflammatory components in the senescence-associated secretory phenotype in premature senescent hepatocytes induced by hexavalent chromium
摘要
Abstract
Objective To investigate the regulation of the inflammatory components interleukin-6 and inter-leukin-8 in the senescence-associated secretory phenotype(SASP)of premature senescent L02 hepatocytes induced by hexavalent chromium Cr(Ⅵ)and their biological roles.Methods L02 hepatocytes were treated with 10 nmol/L Cr(Ⅵ)continuously for 4 weeks and three times a week for 24 h.The control group was treated with phosphate buffer saline.Apply SA-β-Gal staining and detecting age-related proteins to clarify the occur-rence of premature aging.Reactive oxygen species and mitochondrial respiratory transport chain complex(MRCC)kits were used to detect the expression of reactive oxygen species and MRCC Ⅰ and MRCC Ⅱ.ELI-SA kits were used to detect the expression of interleukin-6 and interleukin-8.Cell proliferation curves were plotted to detect the effect of SASP inflammatory components on the proliferative capacity of HCC LM3 cells and senescent cells.Results After 4 weeks of treatment with 10 nmol/L Cr(Ⅵ),L02 hepatocytes showed a large number of positive senescent cells by SA-β-Gal staining and the expression of senescence-related pro-teins SMP30,FN1 and Apo J was significantly increased(P<0.05).Cr(Ⅵ)induced a large amount of reactive oxygen species production in L02 hepatocytes by inhibiting MRCC Ⅰ and MRCC Ⅱ activities(P<0.05),lead-ing to the development of premature cell failure and secretion of inflammatory components interleukin-6 and interleukin-8.p-p65,p65,p-IκBα,and IκBα protein expressions of nuclear factor-κB pathway were elevated(P<0.05).The secretion of inflammatory components interleukin-6 and interleukin-8 by premature senes-cence L02 hepatocytes promoted HCC LM3 cells proliferation.Conclusion Cr(Ⅵ)induced premature senes-cence in L02 hepatocytes through the reactive oxygen species/nuclear factor-κ B pathway and regulated the secretion of inflammatory components interleukin-6 and interleukin-8 by SASP,and interleukin-6 and inter-leukin-8 secreted by senescent cells could promote the proliferation of HCC LM3 cells.关键词
六价铬/细胞早衰/衰老相关分泌表型/白细胞介素-6/白细胞介素-8Key words
hexavalent chromium/premature senescence/senescence-associated secretory phenotype/interleu-kin-6/interleukin-8分类
医药卫生引用本文复制引用
肖元元,曾元,马羽,肖芳..重金属六价铬暴露后早衰肝细胞分泌表型中炎性成分的作用研究[J].兰州大学学报（医学版）,2023,49(10):26-31,6.基金项目
中南大学研究生自主探索创新项目(2020zzts239) （2020zzts239）
