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目的探讨转化生长因子β(TGF-β)/Smads信号蛋白在4.25%的葡萄糖腹膜透析液与脂多糖(LPS)诱导的大鼠腹膜纤维化形成过程中的动态变化及意义。方法 32只SD雄性大鼠(160～170g),随机分为正常对照组(n=8),大鼠不做任何处理;模型组(n=24),每日给予腹腔注射4.25%的葡萄糖腹膜透析液(100ml/kg),同时腹腔注射LPS(0.6mg/kg),每周2～3次,随机分为2周模型组、4周模型组和6周模型组。用光镜观察壁层腹膜组织形态结构,脏层腹膜组织用Western杂交、RT-PCR及间接免疫荧光的方法检测TGF-β1、p-Smad2/3、α-SMA、COL-Ⅰ的表达水平。结果 HE、Masson染色显示,各模型组壁层腹膜组织较正常组明显增厚(P<0.05),间皮下有胶原的沉积。2周、4周和6周模型组与正常组比较TGF-β1、p-Smad2/3、α-SMA及COL-Ⅰ表达明显增强(P<0.05),且随着时间的延长出现了一些动态变化。结论腹腔注射4.25%的葡萄糖腹膜透析液与LPS2周可成功诱导腹膜纤维化模型,TGF-β/Smads信号蛋白的活化是葡萄糖腹膜透析液与LPS诱导大鼠发生腹膜纤维化的生物学基础,随着时间的延长,腹膜纤维化持续存在且缓慢进展,这为我们进一步探讨腹膜纤维化治疗问题时,选择治疗靶点奠定了模型基础。
Objective To investigate the dynamic changes of transforming growth factor β (TGF-β) / Smads signaling in the formation of peritoneal fibrosis induced by 4.25% glucose peritoneal dialysis solution and lipopolysaccharide (LPS) in rats. Methods 32 SD male rats (160-170 g) were randomly divided into normal control group (n = 8), rats without any treatment; model group (n = 24), intraperitoneal injection of 4.25% glucose peritoneum Dialysate (100ml / kg) and intraperitoneal injection of LPS (0.6mg / kg) 2 ~ 3 times a week were randomly divided into 2 weeks model group, 4 weeks model group and 6 weeks model group. The morphology of parietal peritoneum was observed with light microscope. The visceral peritoneum of visceral tissues was examined by Western blot, RT-PCR and indirect immunofluorescence. The expression of TGF-β1, p-Smad2 / 3, α-SMA and COL- Results HE and Masson staining showed that the parietal peritoneal tissue in each model group was significantly thicker than the normal group (P <0.05), and there was collagen deposition in the mesothelium. The expressions of TGF-β1, p-Smad2 / 3, α-SMA and COL-Ⅰ in the model group at 2 weeks, 4 weeks and 6 weeks were significantly higher than those in the normal group (P <0.05) Variety. Conclusion Intraperitoneal injection of 4.25% glucose peritoneal dialysis solution and LPS for 2 weeks can induce peritoneal fibrosis model. The activation of TGF-β / Smads signal protein is the biological basis of peritoneal fibrosis induced by glucose peritoneal dialysis solution and LPS in rats. With the extension of time, persistent and slow progress of peritoneal fibrosis, which for our further discussion of the treatment of peritoneal fibrosis, the choice of treatment targets laid the foundation for the model.