肿瘤坏死因子、内皮素和一氧化氮在肝硬化大鼠门静脉高压高动力循环综合征中作用的研究

Role of tumor necrosis factor, endothelin and nitric oxide in hyperdynamic circulatory syndrome in cirrhotic portal hypertensive rats

目的 了解肿瘤坏死因子 (TNF)、内皮素 (ET)和一氧化氮 (NO)在门静脉高压高动力循环综合征 (HCS)中的作用和地位以及门静脉血中含量的高低对HCS的影响。方法 四氯化碳诱导肝硬化大鼠在用抗TNF抗体 ,一氧化氮合成酶 (NOS)抑制剂NG 甲基 L 精氨酸处理前后测定门脉血TNF ,ET和NO含量及肝组织NOS活性 ,同时监测血流动力学。结果 肝硬化大鼠门脉血中TNF ,NO水平显著增高 ,ET也有轻度上升 ,肝组织NOS活性显著增高。在注射抗TNF抗体后 ,门脉血中TNF含量显著下降至对照水平 ,ET水平无变化 ,肝组织NOS活性较处理前下降 15 %～30 % ,同时HCS部分缓解。在注射NG 甲基 L 精氨酸后 ,门脉血NO含量及肝组织NOS活性显著降低至对照水平 ,HCS明显缓解 ,门脉压力降至正常范围。结论 NO在HCS形成中起关键作用 ,TNF可能通过激活NOS使NO升高而发挥作用 ,ET与HCS形成无直接因果关系。

Objective To investigate the role of tumor necrosis factor (TNF), endothelin (ET) and nitric oxide (NO) in hyperdynamic circulatory syndrome (HCS) of portal hypertension and the effects of their levels on HCS. Methods The quantities of TNF, ET and NO in the blood of portal vein and the activity of nitric oxide synthase (NOS) in hepatic tissue were determined by pre and post injection of anti rat TNF and L NMMA, an inhibitor of NOS. The hemodynamic features were supervised simultaneously in carbon tetrachloride induced cirrhotic portal hypertensive rats. Results The levels of TNF and NO and activity of NOS were significantly increased while that of ET slightly increased in this kind of rat model. After the injection of anti rat TNF, the level of TNF was significantly decreased. There was no change in ET level. The activity of NOS was decreased for 15%～30% and HCS partially ameliorated. After the injection of L NMMA, the level of NO and activity of NOS were markedly decreased. HCS was obviously relieved. Meanwhile, portal pressure was decreased to normal range. Conclusions NO plays a critical role in formation of HCS. TNF may plays a indirect role in the formation by increasing NO level through activating NOS. No direct relationship is found between ET and HCS.