罗格列酮调控PPARγ/HO-1的表达抑制肝星状细胞增殖  

Rosiglitazone inhibits hepatic stellate cell proliferation by regulating peroxisome proliferator-activated receptor gamma/heme oxygenase-1 expression

作　　者：杨慧[1] 赵龙凤[1] 张丽[1] 张晓华 张晓倩 Yang Hui;Zhao Longfeng;Zhang Li;Zhang Xiaohua;Zhang Xiaoqian(Department of Infectious Diseases,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院感染病科,太原030001

出　　处：《中华肝脏病杂志》2020年第5期410-415,共6页Chinese Journal of Hepatology

基　　金：山西省重点研发计划(国际合作类)科研项目(201803D421064);山西省卫生计生委科研项目(201601030)。

摘　　要：目的探讨罗格列酮(RGZ)对肝星状细胞(HSCs)中过氧化酶体增殖物激活受体γ(PPARγ)及血红素加氧酶-1(HO-1)表达的影响。方法以体外活化的肝星状细胞(HSC-T6)为研究对象,分为:空白对照组、RGZ干预组、RGZ与锌原卟啉-Ⅸ(ZnPP-Ⅸ)共同干预组。采用四甲基偶氮唑盐法检测HSC-T6的增殖情况,酶联免疫吸附试验检测细胞上清液中透明质酸(HA)及Ⅲ型前胶原肽(PⅢP)含量,实时荧光定量PCR、蛋白质印迹法及免疫细胞化学技术检测PPARγ、HO-1的mRNA及蛋白相对表达水平。多组间样本均数的比较采用单因素方差分析,组间比较采用LSD检验。结果RGZ干预组HSC-T6增殖活性及HA、PⅢP表达较空白对照组显著下降(P值均<0.01),但PPARγ、HO-1的mRNA及蛋白相对表达量均较空白对照组显著增加(PPARγ:2.97±0.22对比1.07±0.05,0.96±0.08对比0.31±0.03;HO-1:4.28±0.73对比1.80±0.36,1.83±0.26对比0.61±0.09),P值均<0.01,差异有统计学意义。RGZ与ZnPP-Ⅸ共同干预组同RGZ干预组比较,HSC-T6增殖活性及HA、PⅢP表达有所升高(P值均<0.05);HO-1的的mRNA相对表达量(3.16±0.38对比4.28±0.73)和蛋白相对表达水平(1.31±0.17对比1.83±0.26)降低,P值均<0.05,差异有统计学意义;PPARγ的mRNA及蛋白相对表达量比较,差异无统计学意义(P值均>0.05),但呈下降趋势。RGZ与ZnPP-Ⅸ共同干预组与空白对照组HO-1的mRNA相对表达量(1.80±0.36)及蛋白相对表达量(0.61±0.09)比较,明显增高,P值均<0.05。免疫细胞化学染色同上述结果一致。结论罗格列酮诱导PPARγ表达增加进而抑制HSC增殖活化及胶原产生的作用可能是通过调控其下游HO-1的表达而实现的。Objective To investigate the effect of rosiglitazone(RGZ)on the expression of peroxisome proliferator-activated receptor gamma(PPARγ)and heme oxygenase-1(HO-1)in hepatic stellate cells(HSCs).Methods In vitro activated hepatic stellate cell-T6(HSC-T6)as research subjects were divided into blank control group,RGZ intervention group,and RGZ+ZnPP-IX mutual intervention group.MTT colorimetry method was used to measure the condition of cell proliferation.ELISA was used to detect the content of hyaluronic acid(HA)and type III procollagen peptide(PIIIP)in the cell supernatant.Real-time quantative PCR,western blot and immunocytochemistry were used to detect the relative expression levels of PPARγ,HO-1 mRNA and protein.One-way analysis of variance was used to compare the sample mean between multiple groups,and LSD test was used for comparison between two groups.Results The proliferation activity of HSC-T6 and the expressions of HA and PIIIP in the RGZ intervention group were significantly lower than those in the blank control group(P<0.01),but the relative expression levels of PPARγand HO-1 mRNA and protein were significantly increased compared with the blank control group(PPARγ:2.97±0.22 vs.1.07±0.05,0.96±0.08 vs.0.31±0.03;HO-1:4.28±0.73 vs.1.80±0.36,1.83±0.26 vs.0.61±0.09),and the difference was statistically significant(P<0.01).The proliferation activity of HSC-T6 and the expression of HA and PIIIP was higher in RGZ+ZnPP-IX mutual intervention group as compared with RGZ group(P<0.05).HO-1 mRNA(3.16±0.38 vs.4.28±0.73)and protein(1.31±0.17 vs.1.83±0.26)relative expression levels was decreased,and the difference was statistically significant(P<0.05).There was no statistically significant difference in the relative expression of PPARγmRNA and protein(P>0.05),however,there was a decreasing trend.HO-1 mRNA(1.80±0.36)and protein(0.61±0.09)relative expression was significantly increased in RGZ+ZnPP-IX group as compared to blank control group(P<0.05).Immunocytochemical staining had consistency with the above r

关 键 词：血红素加氧酶-1 肝星状细胞 罗格列酮 过氧化酶体增殖物激活受体γ 

分 类 号：R575.2[医药卫生—消化系统]