沙利度胺对门脉高压大鼠腹水形成的影响

Effect of thalidomide on ascites formation in portal hypertensive rats

目的探讨沙利度胺(thalidomide,T)和血管内皮生长因子(vascular endothelial growth factor,VEGF)对门脉高压大鼠腹水形成的影响。方法雄性SD大鼠随机分为3组:门静脉结扎(portal vein ligation,PVL)组20只,假手术(sham-operated,SO)组10只,门静脉结扎联合沙利度胺治疗(PVL-T)组10只。为诱导腹水形成,于手术后第3天分别给予每只大鼠腹腔注射33.33%葡萄糖溶液1 mL,30 min后收集腹水标本并测总量,同时采用ELISA测定腹水中VEGF含量;留取肠系膜组织作VEGF免疫组化染色和实时RT-PCR。结果PVL组大鼠腹水总量和VEGF含量显著大于SO组(P<0.05),PVL-T组腹水总量显著低于PVL组(P<0.05)。组织学结果表明PVL组肠系膜可见较多扩张血管,免疫组化结果显示PVL组VEGF呈强阳性表达,而SO组VEGF则呈弱阳性表达,且表达部位多在血管内皮细胞胞浆;实时RT-PCR结果表明肠系膜VEGF mRNA表达在PVL-T组显著降低(P<0.05)。结论门静脉高压可增加由于渗透性改变所致大鼠腹水形成,VEGF高表达可能与大鼠腹水形成有关。

Objective To study the effect of thalidomide and vascular endothelial growth factor（VEGF） on ascites formation in portal hypertensive rats. Methods Male SD rats were randomly divided into three groups： portal vein ligation（PVL） group with 20 rats,sham-operated（SO） group with 10 rats,portal vein ligation combined with thalidomide treatment（PVL-T） group with 10 rats.In order to induce the formation of ascites,1.0 mL of 33.33% glucose was injected into abdomen of every rat in 3 days after operation.Ascites and mesentery were collected after 30 minutes injection of glucose solution.VEGF levels in ascites were measured by ELISA.Expression of VEGF in tissues was detected by real-time RT-PCR and immunohistochemistry. Results The amount of ascites and VEGF levels in PVL rats were significantly higher than those in SO rats（P0.05）.After operation 3 days,the amount of ascites in PVL-T group was significantly lower than that in PVL group（P0.05）.Histological results showed that many dilated collateral veins were recognized in the mesentery of PVL rats.The endothelium of the veins was immunohistochemically strong positive for anti-VEGF in PVL rats.Real-time RT-PCR also showed that the expression of VEGF mRNA of mesentery in PVL-T group was significantly lower than that in PVL group（P0.05）. Conclusion Portal hypertension increases ascites formation which is caused by a difference of osmolality.Increased expression of VEGF may be associated with ascites formation in portal hypertensive rats.