利拉鲁肽联合锌alpha2糖蛋白对棕榈酸诱导的HepG2细胞凋亡、脂质代谢和炎症因子表达的影响  

Effects of liraglutide combined with ZAG on palmitic acid-induced apoptosis,lipid metabolism and expression of inflammatory factors in HepG2 cells

作　　者：范明娟[1] 聂玉强[1] 詹琪[1] 李洁[1] FAN Mingjuan;NIE Yuqiang;ZHAN Qi;LI Jie(Department of Geriatrics,Guangzhou Frist People′s Hospital,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院老年病科,广州510180

出　　处：《实用医学杂志》2021年第22期2856-2861,共6页The Journal of Practical Medicine

基　　金：广东省自然科学基金项目(编号:2016A030310110)。

摘　　要：目的探讨利拉鲁肽联合锌alpha2糖蛋白(ZAG)对棕榈酸诱导的HepG2细胞凋亡、脂质代谢和炎症因子表达的影响。方法实时定量PCR(RT-qPCR)和蛋白质印迹法分析ZAG在非酒精性脂肪性肝病(NALFD)患者肝组织以及棕榈酸诱导的HepG2细胞中的表达水平。将HepG2细胞分为对照组、棕榈酸组、棕榈酸+利拉鲁肽组、棕榈酸+pcDNA-ZAG组、棕榈酸+利拉鲁肽+ZAG shRNA组、棕榈酸+利拉鲁肽+pcDNA-ZAG组。流式细胞术分析细胞凋亡情况。试剂盒测定细胞中总胆固醇(TC)、甘油三酯(TG)水平,同时测定细胞培养液上清中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平。结果NALFD患者肝组织中ZAG mRNA和ZAG蛋白表达水平显著降低(P <0.05)。棕榈酸处理显著下调ZAG mRNA和ZAG蛋白表达,增加TC、TG、IL-6和TNF-α水平,增加HepG2细胞凋亡率(P <0.05)。利拉鲁肽处理或过表达pcDNA-ZAG显著抑制棕榈酸诱导的HepG2细胞凋亡,并降低TC、TG、IL-6和TNF-α水平(P <0.05)。沉默ZAG显著减弱利拉鲁肽对棕榈酸诱导的HepG2细胞凋亡、TC、TG、IL-6和TNF-α水平的影响(P <0.05)。过表达ZAG显著增强利拉鲁肽对棕榈酸诱导的HepG2细胞凋亡、TC、TG、IL-6和TNF-α水平的影响(P <0.05)。结论利拉鲁肽联合ZAG可抑制棕榈酸诱导的HepG2细胞凋亡、脂质沉积和炎症反应。Objective To investigate the effect of liraglutide combined with zinc alpha2 glycoprotein(ZAG)on palmitic acid-induced HepG2 cell apoptosis,lipid metabolism and the expression of inflammatory factor.Methods Real-time quantitative PCR(RT-qPCR)and western blotting were used to analyze the expression levels of ZAG in liver tissues of patients with non-alcoholic fatty liver disease(NALFD)and palmitic acid-induced HepG2 cells. HepG2 cells were divided into control group,palmitic acid group,palmitic acid + liraglutide group,palmitic acid + pcDNA-ZAG group,palmitic acid + liraglutide + ZAG shRNA group,palmitic acid + liraglutide + pcDNAZAG group. Cell apoptosis was detected by flow cytometry. Kit was applied to determine the levels of total cholesterol(TC)and triglycerides(TG)in the cells,as well as the levels of interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in the supernatant of the cell culture medium. Results The expression of ZAG mRNA and ZAG protein in liver tissues of NALFD patients was significantly reduced(P < 0.05). Treatment with Palmitic acid significantly down-regulated the expression of ZAG mRNA and ZAG protein,increased the levels of TC,TG,IL-6 and TNF-α,and increased the apoptosis rate of HepG2 cells(P < 0.05). Treatment with liraglutide or over-expression of pcDNAZAG significantly inhibited palmitic acid-induced apoptosis of HepG2 cells,and reduced the levels of TC,TG,IL-6 and TNF-α(P < 0.05). Silencing ZAG significantly weakened the effect of liraglutide on palmitic acid-induced apoptosis,TC,TG,IL-6 and TNF-α levels in HepG2 cells(P < 0.05). Over-expression of ZAG significantly enhanced the effect of liraglutide on palmitic acid-induced apoptosis,TC,TG,IL-6 and TNF-α levels in HepG2 cells(P < 0.05). Conclusion Liraglutide combined with ZAG can inhibit palmitic acid-induced apoptosis,lipid deposition and inflammatory reaction in HepG2 cells.

关 键 词：利拉鲁肽 锌alpha2糖蛋白 棕榈酸 HEPG2细胞 凋亡 炎症 甘油三酯 

分 类 号：R575.1[医药卫生—消化系统]