全反式维甲酸对大鼠腹膜透析模型腹膜TGF-β1和COL-Ⅰ表达的影响

Effects of All-trans Retinoic Acid on the Expression of TGF-β1 and COL-Ⅰ in Rat Model of Peritoneal Dialysis

目的研究全反式维甲酸(ATRA)对大鼠腹膜透析模型腹膜转化生长因子-β1(TGF-β1)和胶原(COL-Ⅰ)表达的影响,初步探讨其对腹膜纤维化的作用机制。方法建立大鼠腹膜透析模型,ATRA2mg/kg(小剂量组)、5mg/kg(大剂量组)每日腹腔内注射进行干预,在实验第28d取腹膜组织进行Masson染色,免疫组织化学检测TGF-β1、COL-Ⅰ在脏层腹膜的表达;RT-PCR检测TGF-β1mRNA的表达。结果Masson染色显示,模型组腹膜较对照组明显增厚,胶原大量沉积;ATRA治疗组腹膜病变均有不同程度减轻。免疫组化和RT-PCR结果表明,模型组腹膜组织中TGF-β1和COL-Ⅰ的表达明显高于对照组,小、大剂量ATRA组表达均显著降低,且大剂量组较小剂量组表达低。结论ATRA可以下调TGF-β1的表达和抑制COL-Ⅰ的合成,延缓腹膜纤维化的进展。

Objective To investigate the effects of all-trans retinoic acid（ATRA）on the expression of transforming growth factor-β1（TGF-β1）and collagen Ⅰ（COL-Ⅰ）in rat model of peritoneal dialysis,which may relate to the prevention peritoneal fibrosis.Methods Peritoneal dialysis model was estabolished in rats,and then the rats were given ATRA 2 mg/kg（small dose group）or 5 mg/kg（large dose group）by the way of intraperitoneal injection once a day.All the rats were sacrificed on day 28.TGF-β1 and COL-Ⅰprotein expression of peritoneum were measured by immunohistochemistry.TGF-β1 mRNA expression were examined with real time polymerase chain reaction（RT-PCR）.Results Masson stain showed that the peritoneum thickness was significantly increased in the rats model,and collagen deposition was evident in the thickened submesothelial compact zone.With the treatment of ATRA,either in small or large dose,pathological changes were significantly lessened.The expression of TGF-β1 and COL-Ⅰ of peritoneum was increased significantly in the rats model,but the levels in the two ATRA treated groups were lower than those of the untreated group.Conclusion ATRA could decrease the experession of TGF-β1 and COL-Ⅰin peritoneum and delay the progression of peritoneal fibrosis.