血管内皮生长因子在门静脉高压大鼠腹水形成中的作用

Role of vascular endothelial growth factor on ascites formation in portal hypertensive rats

目的探讨血管内皮生长因子（VEGF）在门静脉高压大鼠腹水形成中的作用。方法将雄性SD大鼠随机分为3组：门静脉结扎（PVL）组32只,假手术（SO）组16只,门静脉结扎联合沙利度安治疗（PVL-T）组8只。为诱导腹水形成,于手术后第1、3、5、7天分批给予每只大鼠腹腔注射33.33%葡萄糖溶液1mL,30min后收集腹水标本并测总量,同时采用ELISA检测腹水中VEGF含量;留取肠系膜组织作VEGF免疫组化染色和实时RT-PCR检测。结果术后第1、3天PVL组大鼠腹水总量和VEGF含量明显大于SO组（P〈0.05）,术后第5、7天PVL组大鼠腹水总量和VEGF含量与SO组比较,差异无统计学意义（P〉0.05）,术后第3天PVL-T组腹水总量明显低于PVL组[分别为（3.4±0.27）mL、（4.92±1.53）mL,P〈0.05）]。组织学检查PVL组肠系膜可见较多扩张血管。PVL组VEGF呈强阳性表达,而SO组VEGF则呈弱阳性表达,且表达部位多为血管内皮细胞胞浆;PVL-T组肠系膜VEGFmRNA表达明显降低（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 role of vascular endothelial growth factor on ascites formation in portal hypertensive rats.Methods Male S-D Rats were randomly divided into three groups：portal vein ligation（PVL）group with 32rats,sham-operated（SO）group with 16rats,portal vein ligation combined with thalidomide treatment（PVL-T）group with 8rats.To induce the formation of ascites,1.0mL of 33.33%glucose was injected into abdomen of every rats in 1,3,5,7days after operation.Ascites and mesentery was collected 30minutes after injection of glucose solution.VEGF levels in ascites were measured by ELISA.Expression of VEGF in tissues was studied using real-time RT-PCR and immunohistochemistry.Results 1day,3days after operation,the amount of ascites and VEGF level in PVL rats was significantly higher than that in SO rats（P〈0.05）.whereas,5days,7days after operation,the amount of ascites and VEGF concentration had no significant difference between the PVL group and the SO group（P〈0.05）.3days after operation,the amount of ascites in PVL-T group was significantly lower than that in PVL group（3.4±0.27 mL vs 4.92±1.53mL,P〈0.05）.Histological results showed that Many dilated collateral veins were recognized in the mesentery of PPVL rats.The endothelium of the veins was immunohistochemically strong positive for anti-VEGF in PVL rats.Real-time RTPCR results also showed that VEGF-mRNA expression of mesentery in PVL-T group was significantly lower than that in PVL group（P〈0.05）.Conclusion Portal hypertension increases ascites formation which is caused by a difference of osmolality.Increase expression of VEGF may be associated with ascites formation in portal hypertensive rats.Suppression of VEGF activity maybe a new strategy for treatment of refractory ascites in cirrhotic patients.