吡格列酮对转化生长因子β诱导的大鼠肝星状细胞的影响

目的观察吡格列酮对TGFβ诱导的大鼠HSC形态和结缔组织生长因子(CTGF)表达的影响,探讨吡格列酮抑制肝纤维化的机制。方法将大鼠HSC进行体外培养,并分为空白组、TGFβ组、TGFβ 不同剂量吡格列酮组。观察HSC细胞发生的形态学改变,并用免疫组织化学、流式细胞仪定性及定量检测CTGF的表达;ELISA法测定培养细胞上清液中Ⅲ型胶原的含量。结果TGFβ可以诱导大鼠HSC细胞形态发生改变和表达CTGF,且TGFβ组细胞上清液中Ⅲ型胶原含量增加(P<0.05);吡格列酮组可以不同程度抑制TGFβ诱导的细胞形态学改变,各组CTGF的表达水平以及Ⅲ型胶原分泌均低于TGFβ组(P<0.05),且呈剂量依赖性(P<0.05)。结论吡格列酮能够抑制TGFβ诱导的大鼠HSC细胞形态改变、CTGF表达及Ⅲ型胶原的分泌,对肝纤维化具有抑制作用。

Effects of pioglitazone on the morphology and the expression of connective tissue growth factor of transforming growth factor beta-induced rat hepatic stellate cells in vitro

OBJECTIVES: To observe the effects of pioglitazone on morphological changes and connective tissue growth factor (CTGF) expression of the transforming growth factor beta (TGF b)-induced rat hepatic stellate cells (HSCs) in vitro, and to investigate the anti-fibrotic mechanism of pioglitazone. METHODS: Cultured rat HSCs were divided into a no-treatment control group, a TGF b-treated group, and a TGFb plus different dosage pioglitazone-treated group. The morphological changes of the cultured HSCs were observed. The expression of CTGF was assessed by immunohistochemistry and flow cytometry. The level of collagen type III in the culture supernatant was measured by ELISA. RESULTS: TGFb induced morphological changes, and increased the expressions of CTGF and collagen type III of the HSCs (P less than 0.05). Pioglitazone prevented the TGFb induced morphological changes of the HSCs. The expression of CTGF and the levels of collagen type III in the pioglitazone group were lower than the TGF b-treated group (P less than 0.05). This prevention effect was dose-dependent (P less than 0.05). CONCLUSION: Pioglitazone blocks the excretion of CTGF and collagen type III of cultured HSCs, preventing the development of liver fibrosis.