一氧化氮在大鼠肝硬变门静脉高压症形成中的作用及其对血液动力学的影响

Nitric oxide in pathogenesis of cirrhotic portal hypertension in rats and its hemodynamic effects

目的探讨一氧化氮（ＮＯ）在肝硬变门静脉高压症（ＰＨＴ）形成过程中的作用。方法采用比色法和鲎试验改良基质显色法，对大鼠肝硬变ＰＨＴ形成过程中，外周血ＮＯ、内毒素浓度和血液动力学的变化进行检测，观察了ＮＯ合成酶抑制剂Ｌ－ＮＭＭＡ对ＰＨＴ大鼠血液动力学的影响。结果（１）在大鼠肝硬变ＰＨＴ形成过程的早、中、晚三期，血浆ＮＯ和内毒素水平显著升高。（２）在肝硬变形成各期门静脉阻力（ＰＶＲ）和门静脉压力（ＰＶＰ）均显著升高，平均动脉压（ＭＡＰ）和内脏血管阻力（ＳＶＲ）显著下降，门静脉血流量（ＰＶＦ）变化不明显。（３）ＮＯ水平和内毒素、ＰＶＰ呈显著正相关。（４）注射Ｌ－ＮＭＭＡ，肝硬变大鼠ＭＡＰ、ＳＶＲ、ＰＶＲ显著升高；ＰＶＦ显著下降；ＰＶＰ变化不明显。结论ＮＯ参与了ＰＨＴ时高动力循环状态的形成。

Objective To measure serum nitrite and nitratre levels as an index for in vivo nitric oxide generation in rats at different stages during the development of cirrhosis with portal hypertension. Method Plasma endotoxin and hemodynamic parameters were measured. The effects of NO monomethl L arginine (L NMMA),an inhibitor of NO biosynthesis were investigated in rats with cirrhosis. Result Significant increase was noted in serum nitrite/nitrate and plasma endotoxin compared with controls at each stage of cirrhosis. At each stage, the mean arterieal pressure(MAP) and splanchnic vascular resistance (SVR) were significantly lower than those of controls, whereas portal venous pressure (PVP) and portal vascular resistance (PVR) significantly increased and portal venous flow (PVF) was not markedly different from that of the controls. In addition, the serum nitrite/nitrate levels significantly were correlated with endotoxemia and PVP.Intravenous bolus administration of L NMMA(25mg/kg) significantly increased MAP、PVR and SVR in cirrhotic rats. L NMMA also significantly decreased PVF but did not alter PVP and IVCP. Conclusion The excessive synthesis and release of NO plays a key role in the induction of portal hypertension.