沙利度胺对大鼠肝纤维化细胞黏附分子表达的影响

Effect of thalidomide on the expression of cell adhesion molecules in fibrotic rats

目的研究沙利度胺对实验性大鼠肝纤维化的疗效和细胞间黏附分子-1(ICAM-1)、血管细胞间黏附分子-1(VCAM-1)、E-选择素(E-selectin)在其中的作用。方法四氯化碳腹腔注射制备大鼠肝纤维化模型后,应用沙利度胺(100mg/kg)灌胃分别治疗2、4、6周作为动态观察时相点。观察肝组织病理学变化;放射免疫法检测血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(CⅣ)的表达;免疫组织化学方法检测ICAM-1、VCAM-1、E-selectin的表达。结果与肝纤维化组相比,沙利度胺治疗4周组、6周组可显著改善大鼠肝组织病理学变化,显著降低血清HA、LN、PCⅢ、CⅣ的含量(P<0.05)。沙利度胺治疗2周组、4周组、6周组均可显著降低肝组织ICAM-1、VCAM-1、E-selectin蛋白表达(P<0.05)。结论沙利度胺可以逆转大鼠肝纤维化,机制可能与其抑制黏附分子的表达有关。

Objective To study the therapeutic effect of thalidomide on liver fibrosis in rats and its effect on the expression of ICAM-1 ,VCAM-1 and E-selectin.Metbods Liver fibrosis of rat was induced by intraperitoneal injection with carbon tetrachloride （CCl4） for 4 weeks. The dynamic change of liver fibrosis were observed at different time points（2wk, 4wk, 6wk after using 100mg/kg thalidomide by intragastric administration） . The histopathology of liver was examined by HE staining. Serum hyaluronic acid（HA）, laminin （LN）, procollagen type Ⅲ （PC Ⅲ ） and collagen type Ⅳ（ C Ⅳ ） were detected by radioimmunoassay. The expression of ICAM-1, VCAM-1 and E-selectin were examined by immunohistochemistry staining. Resuits Compared with the liver fibrosis group, thalidomide（4 weeks or 6 weeks） improved the liver histopathological alteration significantly. Serum HA, LN, PC Ⅲand C Ⅳof the rats in the group-treated with thalidomide for 4 weeks or 6 weeks were significantly lower than those in liver fibrosis group （ P 〈 0.05） . The expressions of ICAM-1, VCAM-1 and E-selectin protein were significantly reduced in thalidomide-treated groups （2 weeks, 4 weeks, or 6 weeks）, compared with those in liver fibrosis group （ P 〈 0.05）. Conclusion Thalidomide can effectively reverse the liver fibrosis of rats. Its effect on the expression of Ⅰ- CAM-1, VCAM-1 and E-selectin may be one of its mechanisms.