【摘要】 目的探讨过氧化物酶增殖物激活受体γ（PPARγ）对大鼠肝星状细胞（HSC）增殖与凋亡的影响。方法常规培养大鼠HSC,经系列浓度的PPARγ天然配体（15-d-PGJ2）或合成配体（GW7845）作用后,通过噻唑蓝（MTT）比色法及流式细胞仪观察细胞的增殖和凋亡状态,应用半定量逆转录-聚合酶链反应（RT-PCR）和Western blot探讨PPARγ配体诱导凋亡的分子机制,透射电镜观察HSC形态学变化。结果15-d-PGJ₂和GW7845可通过抑制细胞增殖同时诱导凋亡而抑制HSC生长,且呈剂量依赖效应（各实验组与对照组比较,P＜0．01）；PPARγ活化可显著抑制HSC中bcl-2基因表达（同时在转录和转录后水平）,且此抑制作用可被PPARγ特异性拮抗剂GW9662部分或完全逆转,说明此种抑制效应确由PPARγ所介导；电镜观察亦显示明显的细胞凋亡发生。结论PPARγ活化可显著抑制HSC增殖,并通过下调bcl-2基因表达而诱导凋亡,提示PPARγ可作为逆转肝纤维化治疗的新的有效靶点。更多还原

【Abstract】 Objective To investigate the effect of activation of peroxisome proliferator-activated receptor gamma（PPARγ）on cell proliferation and apoptosis in rat hepatic stellate cells（HSC）.Methods After treated with an increasing amount of PPARγnatural ligand 15-d-PGJ₂ or synthetic ligand GW7845,the HSC proliferation and apoptosis were detected by MTT assay and flow cytometry respec- tively.HSC were pretreated with or without PPARγ-specific antagonist GW9662 prior to the addition of 15-d-PGJ₂ or GW7845.The mRNA and protein levels of bcl-2 expression were detected by semi-quantita- tive RT-PCR and Western-blotting analysis.The morphological changes of HSC were observed under an electron microscope.Results 15-d-PGJ₂ and GW7845 could markedly inhibit HSC proliferation and in- duce cell apoptosis in a dose-dependent manner（P＜0.01）.PPAR7 ligands could significantly suppress bcl-2 expression（at both transcriptional and post-transcriptional levels）in HSC and the inhibitory effect was dramatically,if not completely,abolished by pretreatment with GW9662,suggesting that the inhibi- tion was indeed mediated by PPARγ.Morphological observation revealed that PPARγactivation caused obvious apoptosis in HSC.Conclusion PPARγligand showed potent inhibitory effect on the growth of HSC,which made it a potential antifibrotic candidate for treatment and prevention of hepatic fibrosis.更多还原