硫化氢对肝硬化大鼠肝脏survivin表达的影响

Effect of hydrogen sulfide on the expression of survivin in the liver of rats with hepatic cirrhosis

目的:探讨抗凋亡因子存活素(survivin)在硫化氢(hydrogen sulfide,H2S)干扰的肝硬化大鼠肝脏中的表达量,了解H2S在肝硬化过程中可能的作用机制.方法:♀SD大鼠经复合因素法复制肝硬化模型,造模结束后随机分为S组、P组、C组,分别腹腔注射硫氢化钠(sodium hydrogen sulfide,NaSH)56mg/(kgd)、炔丙基甘氨酸(Propargylglycine,PPG)30mg/(kgd)及等量生理盐水,用敏感硫电极法检测肝硬化大鼠门静脉中H2S的量,用免疫组织化学及realtime-PCR检测大鼠肝脏survivin蛋白及mRNA表达.结果:S组、P组与C组相比,门静脉血浆内H2S浓度显著改变(51.19mol/L±8.75mol/L,68.97mol/L±2.69mol/Lvs134.49mol/L±12.25mol/L,P<0.05),肝硬化H2S增加组大鼠survivin蛋白及mRNA表达显著增加(P<0.05),肝硬化大鼠体内H2S与survivin表达有相关性.结论:在大鼠肝硬化模型中,随着体内H2S浓度的变化,survivin蛋白及mRNA表达发生变化,这可能是H2S调节肝硬化作用过程中的机制之一.

AIM： To examine the expression of anti-apoptosis gene survivin in the liver of rats with hepatic cirrhosis treated with hydrogen sulfide （H 2 S） to understand the role of hydrogen sulfide in the pathogenesis of hepatic cirrhosis. METHODS： Female Sprague-Dawley rats were used to induce hepatic cirrhosis by injecting carbon tetrachloride. The rats were randomly divided into three groups （S, P and C） and injected with sodium hydrogen sulfide （NaSH, 56 mg/（kg d））, propargylglycine （PPG, 30 mg/（kg·d）） and normal saline, respectively. The concentration of H 2 S in portal vein blood was measured by sensitive sulphur electrode assay, and the expression of survivin protein and mRNA in the liver was measured by immunohistochemistry and real time-PCR, respectively. RESULTS： Compared to group S, the concentration of H 2 S in portal vein blood increased significantly （51.19 mol/L ± 8.75 mol/L, 68.97 mol/ L ± 2.69 mol/L vs 134.49 mol/L ± 12.25 mol/L, both P 0.05）, and the expression of survivin protein and mRNA was significantly up-regulated （both P 0.05） in groups P and C. There is a significant correlation between the concentrations of hydrogen sulfide and survivin expression levels in rats with hepatic cirrhosis. CONCLUSION： In rats with hepatic cirrhosis, the changes in the concentrations of H 2 S correlate with the expression of survivin. H 2 S regulates hepatic cirrhosis possibly by modulating the expression of survivin.