肿瘤坏死因子α对兔门静脉高压症形成的作用

Effect of TNF-α on the development of portal hypertension in rabbits

目的 探讨肿瘤坏死因子α(TNFα)在门静脉高压症(PHT)形成过程中的作用。方法 本实验通过门静脉缩窄法制备兔PHT模型,采用MTT法测定对照组、PHT组门静脉缩窄后1,3,7d以及3周时的外周血TNFα水平,并应用电磁血流量计和多导生理记录仪测定其门静脉血流动力学的变化以及一氧化氮(NO)合成抑制剂对PHT血流动力学的影响。结果 PHT组自由门静脉压(FPP)、门静脉血流量(PVF)、门体分流率(PSSRP)以及外周血TNFα水平显著升高(P<0.01);而平均动脉压(MAP)、向肝门静脉血流量(Qpv)、脏侧闭塞门静脉压(SOPP)明显下降(P<0.01)。应用NO合成抑制剂后PHT组PVF明显降低(P<0.01),MAP明显升高(P<0.01),而FPP无明显变化(P>0.05);对照组除MAP明显升高(P<0.01)外,PVF,FPP均无明显变化(P>0.05)。结论 TNFα对PHT血流动力学改变可能起重要作用,NO是介导此过程的主要介质。

Objective To investigate the effect of TNF α on development of portal hypertension (PHT). Methods New Zealand white male rabbits were used to establish PHT model using partial portal vein ligation (PVL). TNF α levels of peripheral blood in both control and PHT groups 1,3,7 days and 3 weeks after PVL were tested by MTT respectively. Changes in hemodynamics of the portal vein in PHT rabbit models before and after infusion of NO synthesis inhibitor were measured by electrical magnetic flow instrument and multiple physiological recorder respctively. Results For PHT group, significant elevation were shown in free portal pressure (FPP), portal vein inflow (PVI), percent portosystemic shunt rate of PVF(PSSRSP) and TNF α levls of peripheral blood were found; while significant decreases (P<0.01) of mean arterial pressure (MAP), hepatopetal portal flow (Qpv), and splanchnic obstructive portal pressure (SOPP). After infusion of the inhibitor of NO synthesis, PVF in PHT group was also significantly reduced (P<0.01) and MAP was significantly elevated (P<0.01), while FPP remained unchanged. Conclusions TNF α possibly plays an importan role in hemodynamic changes in PHT rabbit model, and NO is the key mediator in this process.