PPARγ激活拮抗细菌脂多糖诱发HTR-8细胞炎症的作用  

PPARγprotects against lipopolysaccharide-induced inflammation in HTR-8 cells

作　　者：谢亚莉 林秋琳 孙嘉壮 博庆丽[1] 赵存喜[1] XIE Ya-li;LIN Qiu-lin;SUN Jia-zhuang;BO Qing-li;ZHAO Cun-xi(Department of Nutrition and Food H-ygiene,School of Public Health,Anhui Medical University,Hefei Anhui,230032,China;Clinical Medicine("5+3"integration),Second School of Clinical Medicine,Anhui Medical University,Hefei Anhui,230032,China)

机构地区：[1]安徽医科大学公共卫生学院营养与食品卫生学系,安徽合肥230032 [2]安徽医科大学第二临床医学院临床医学(“5+3”一体化),安徽合肥230032

出　　处：《职业与健康》2022年第9期1177-1180,共4页Occupation and Health

基　　金：国家自然科学基金项目(81803268);安徽省自然科学基金项目(1808085MH257);国家社科基金(18BZX117);安徽医科大学博士科研资助基金(XJ201820);安徽医科大学临床医学“早期接触科研”训练项目(2020-ZQKY-87)。

摘　　要：目的了解过氧化物酶体增殖激活受体γ(peroxisomal proliferators activated receptor gamma,PPARγ)激活对细菌脂多糖(lipopolysaccharide,LPS)诱导人胎盘滋养层细胞炎症信号表达增强的拮抗作用和机制。方法将HTR-8细胞分为对照、RSG(PPARγ激动剂)、LPS、RSG+LPS、RSG+LPS+GW9662(PPARγ拮抗剂)和RSG+LPS+MG132(蛋白酶体抑制剂)6组,采用蛋白免疫印迹法检测各组核蛋白中NF-κB p65的表达水平,采用酶联免疫吸附法检测细胞培养上清液中白细胞介素6(IL-6)和白细胞介素1β(IL-1β)的表达水平。结果与对照组相比,LPS组细胞核蛋白NF-κB p65(105.32±22.95)和细胞上清液炎性因子IL-6[(18.77±2.60)pg/mL]、IL-1β[(23.48±8.37)pg/mL]的表达明显升高(均P<0.01),RSG组无明显改变。RSG+LPS组细胞给予RSG预处理激活PPARγ后,LPS所致NF-κB p65(37.22±17.39)、IL-6[(10.75±0.68)pg/mL]和IL-1β[(8.22±1.13)pg/mL]升高的效应被显著抑制(均P<0.01)。RSG+LPS+GW9662和RSG+LPS+MG132组在分别给予PPARγ拮抗剂GW9662和蛋白酶体抑制剂MG132处理后,RSG预处理降低核蛋白NF-κB p65表达的作用被明显抑制(P<0.01)。结论PPARγ激活通过引起NF-κB p65泛素化降解,从而拮抗人胎盘滋养层细胞的炎症信号表达。Objective To investigate the effect and antagonism of the activation of peroxisomal proliferators activated receptorγ(PPARγ)on the increase of inflammatory signal expression in human placental trophoblast cells induced by lipopolysaccharide(LPS).Methods HTR-8 cells were divided into six groups:control group,RSG(PPARγagonist)group,LPS group,RSG+LPS group,RSG+LPS+GW9662(PPARγantagonist)group and RSG+LPS+MG132(proteasome inhibitor)group.The expression levels of nuclear protein-derived NF-κB p65 were determined by western blot in each group,and the expression levels of cell supernatantderived interleukin 6(IL-6)and IL-1βwere determined by enzyme-linked immunosorbent assay kit.Results Compared with the control group,the expression levels of nuclear protein-derived NF-κB p65(105.32±22.95)and cell supernatant-derived inflammatory factors IL-6[(18.77±2.60)pg/mL]and IL-1β[(23.48±8.37)pg/mL]were significantly increased in the group treated by LPS(all P<0.01).These changes were not found significantly in RSG group.In RSG+LPS group,the increasing effects mediated by LPS on NF-κB p65(37.22±17.39),IL-6[(10.75±0.68)pg/mL]and IL-1β[(8.22±1.13)pg/mL]were significantly inhibited after activating PPARγby pretreatment of RSG(all P<0.01).However,RSG+LPS+GW9662 group and RSG+LPS+MG132 group were treated with GW9662 and MG132(proteasome inhibitor)respectively,then the reducing expression of nuclear protein-derived NF-κB p65 after pretreating by RSG was inhibited significantly(P<0.01).Conclusion The activation of PPARγantagonizes the inflammatory signal expression of human placental trophoblast cells by inducing the ubiquitination of NF-κB p65 subunit.

关 键 词：过氧化物酶体增殖激活受体Γ 细菌脂多糖 泛素化 胎盘炎症 

分 类 号：R446.6[医药卫生—诊断学]