过氧化氢在门静脉高压症大鼠侧支循环建立中的作用

Role of hydrogen peroxide in the formation of portosystemic collaterals in portal hypertension

目的探讨过氧化氢(H2O2)对胆总管结扎诱导的肝硬化门静脉高压症(PHT)大鼠门体侧支循环形成的影响机制。方法胆总管结扎诱导的肝硬化PHT大鼠和假手术组大鼠每天一次腹腔分别注射浓度为10 000 U/kg聚乙二醇过氧化氢酶(PEG-catalase)或生理盐水,共8 d。测定大鼠肠系膜组织H2O2含量,利用彩色微球技术测定门体分流率及相应血流动力学指标。检测大鼠肠系膜组织中血管内皮生长因子(VEGF)及VEGF受体-2(VEGFR-2)蛋白含量。结果肝硬化PHT组大鼠门静脉压力、肠系膜组织H2O2水平及门体分流程度明显高于对照组大鼠。PEG-catalase处理使PHT大鼠门体分流率明显下降,VEGF及VEGFR-2蛋白水平明显降低,内脏高血流动力循环得到明显改善。结论 H2O2在肝硬化PHT内脏高动力循环形成过程中发挥重要作用,这和VEGF介导的血管增生有关。

Objective To explore the role of hydrogen peroxide（H2O2） in the formation of portosystemic collaterals in portal hypertensive（PHT） rats. Methods The bile duct ligation-induced cirrhotic rats and normal rats were treated with polyethylene glycol-catalase（PEG-catalase, 10 000 U/d/kg, ip.） or saline for 8 d. Then the hemodynamic studies were performed using the colored microsphere technique. Protein expressions of vascular endothelial growth factor（VEGF） were determined by Western blotting. The H2O2 level of mesentery was measured with the Hydrogen Peroxide Assay Kit. Results Compared with sham-operated animals, the portal pressure,the production of H2O2 and the formation of portal-systemic collateral vessels were higher in portal hypertensive rats. PEG-catalase administration resulted in a significant decrease in portal-systemic collaterals and a lower expression of VEGF in PHT rats. Conclusion H2O2 plays an important role in the development of the splanchnic hyperdynamic circulation in experimental portal hypertension syndrome, which is associated with VEGF-induced angiogenesis.