螺内酯对肝纤维化大鼠肝窦血管生成的抑制作用  

Spironolactone inhibits hepatic sinusoid angiogenesis in rats with hepatic fibrosis

作　　者：李旭[1] 蔡双明[1] 宁佐伟[1] 李洋[1] 张文雍[1] 张莉莉[1] 

机构地区：[1]南方医科大学南方医院急诊科,广东广州510515

出　　处：《南方医科大学学报》2012年第8期1135-1138,1142,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30871155)~~

摘　　要：目的探讨螺内酯对肝纤维化大鼠肝窦血管生成的抑制作用。方法雄性Wistar大鼠24只,随机分为3组,每组8只大鼠。分组如下:假手术组(Sham组);胆总管结扎组(BDL组),予行胆总管结扎术;螺内酯治疗组(BDL+SP组),于手术后第2天给予螺内酯20 mg/kg灌胃处理,1次/d。于4周后取材。Masson三色染色检测胶原和大鼠的肝组织学改变。运用实时荧光定量聚合酶链反应(Real time-qPCR)检测各组血管内皮生长因子A(VEGF-A)mRNA的表达。运用免疫组织化学技术检测各组血管性假血友病因子(vWF)的表达。结果 BDL+SP组纤维化程度较BDL组低[(2.84±0.44)vs(19.73±3.54),P=0.00],差异有统计学意义;免疫组织化学结果显示:BDL组vWF表达较Sham组增高[(3.08±0.17)vs(0.98±0.11),P=0.00],BDL+SP组较BDL组表达下降[(1.15±0.09)vs(3.08±0.17),P=0.00],差异有统计学意义;在BDL组VEGF-A mRNA的表达增加,BDL+SP组则表达下降[(0.71±0.12)vs(1.75±0.15),P=0.00],差异有统计学意义;且各分组中VEGF-A mRNA的表达与vWF表达呈现显著正相关关系(r=0.890,P=0.000)。结论螺内酯通过抑制肝脏VEGF-AmRNA的表达抑制肝窦毛细血管生成。Objective To investigate the inhibitory effects of spironolactone against hepatic sinusoid angiogenesis in rats with hepatic fibrosis. Methods Twenty-four male Wistar rats were randomly divided into sham-operated group, bile duct ligation （BDL） group, and BDL＋SP group in which the rats received daily spironolactone injection （20 mg/kg） the day after BDL. Four weeks after the operation, the rats were sacrificed for examination of liver histology using Masson staining and the expression of vascular endothelial growth factor A （VEGF-A） mRNA in the liver using real-time quantitative PCR. Immunohistochemistry was used to detect the expression of yon Willebrand factor （vWF） in the hepatic tissues. Results Spironolactone significantly inhibited liver fibrogenesis in rats after BDL （METAVIR liver fibrosis scores 2.84±0.44 vs 19.73± 3.54, P=0.00）. Real-time PCR and immunohistochemistry showed that compared with BDL group, spironolactone treatment significantly inhibited the expression of VEGF-A mRNA （0.71±0.12 vs 1.75±0.15, P=0.00） and vWF （1.15±0.09 vs 3.08-±0.17, P= 0.00） in the liver. The expression of VEGF-A mRNA was highly correlated with the expression of vWF （r=0.890, P=0.000）. Conclusion Spironolactone can inhibit hepatic sinusoid angiogenesis in rats with BDL-induced hepatic fibrosis by inhibiting the expression of VEGF-A.

关 键 词：螺内酯 肝纤维化 血管内皮生长因子 肝窦血管生成 

分 类 号：R575.2[医药卫生—消化系统]