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目的探讨硫化氢供体—硫氢化钠(sodium hydrosulfide,NaHS)对大鼠门静脉高压及内源性一氧化氮(nitric monoxide,NO)/一氧化氮合酶(nitricoxide synthase,NOS)体系的影响。方法将30只健康成年雄性SD大鼠随机分为4组:部分门静脉结扎(partly portal vein ligation,PPVL)组(10只)、PPVL+NaHS组(10只)、假手术组(5只)和正常组(5只)。PPVL组和PPVL+NaHS组行部分门静脉结扎术建立门静脉高压的动物模型。模型制作14天后,分别测定各组大鼠的门静脉压力(PVP)和平均动脉压力(MAP);采用免疫组织化学检测大鼠肝细胞中一氧化氮合酶(NOS2、NOSS)的蛋白水平表达情况,RT-PCR方法检测大鼠肝组织中NOS2和NOS3的mRNA水平的表达情况。结果术后14 d,假手术组和正常组比较,各项检测指标无显著差异,NOS2蛋白及mR-NA水平未见明显表达;NOS3蛋白及mRNA表达水平无显著差异。PPVL组与假手术组比较,PVP明显升高(P<0.05),MAP则下降(P<0.05),PPVL+NaHS组与PPVL组相比较,PVP进一步升高(P<0.05),MAP则进一步降低(P<0.05)。PPVL组和PPVL+NaHS组NOS2在蛋白及mRNA水平均有表达,且后者NOS2蛋白及mRNA表达水平减少(P<0.05)。4组之间NOS3的蛋白及mRNA表达水平则无显著差异。结论H2S参与了门静脉高压的形成与发展,NaHS可以加重门静脉高压,其作用可能与NO/NOS2体系有关。
Objective To investigate the effect of sodium hydrosulfide (NaHS) on the portal hypertension and the nitric oxide monoxide (NO) / nitric oxide synthase (NOS) system in rats. Methods Thirty healthy adult male Sprague Dawley rats were randomly divided into 4 groups: partial portal vein ligation (PPVL) group (10), PPVL + NaHS group (10), sham operation group Normal group (5). PPVL group and PPVL + NaHS group underwent partial portal vein ligation to establish an animal model of portal hypertension. After 14 days, the portal vein pressure (PVP) and mean arterial pressure (MAP) of rats in each group were measured respectively. The expression of NOS2 and NOS in rat hepatocytes was detected by immunohistochemistry The mRNA expression of NOS2 and NOS3 in rat liver tissue was detected by RT-PCR. Results There was no significant difference between the sham operation group and the normal group on the 14th day after operation. There were no significant differences in the expression of NOS2 protein and mR-NA between the sham operation group and the normal group. The expression of NOS3 protein and mRNA showed no significant difference. Compared with sham operation group, PVP increased significantly (P <0.05), MAP decreased (P <0.05), PVP increased further in PPVL + NaHS group compared with PPVL group (P <0.05) Decreased (P <0.05). The protein and mRNA levels of NOS2 in PPVL group and PPVL + NaHS group were both lower than those in PPVL group and NaHS group (P <0.05). There was no significant difference in NOS3 protein and mRNA expression among the 4 groups. Conclusions H2S is involved in the formation and development of portal hypertension. NaHS can aggravate portal hypertension and its effect may be related to NO / NOS2 system.