eNOS基因治疗对肝硬化大鼠肝内血流阻力的影响

Effects of eNOS gene transfer on intrahepatic vascular resistance in cirrhotic rats

目的 探讨内皮性一氧化氮合酶 (endothelialnitricoxidesynthase ,eNOS)对肝硬化大鼠肝内血流阻力 (intrahepaticvascularresistance ,IHVR)和门静脉压力 (portalvenouspressure ,PVP)的影响。方法 (1 )建立原位肝脏灌流模型 (insituliverperfusion ,ISLP) ,观察去甲肾上腺素 (noradrenalin ,NE)、NG 单甲基 L 精氨酸 (NG monomethyl L arginine,L NMMA)和精氨酸 (L arginine ,L Arg)对肝硬化大鼠门静脉灌注压 (portalperfusionpressure,PP)的影响。 (2 )观察活体门静脉注射L NMMA对肝硬化大鼠PVP的影响。结果 (1 )ISLP模型中 ,对照组大鼠灌流液中加入L NMMA后PP对NE的反应性显著增加 ,PP峰值增高至 (2 6 .7± 0 . 9)mmHg ;如预先给予L Arg后再加L NMMA ,PP对NE反应性显著低于单用L NMMA时 ,其PP峰值降为 (2 3 .2± 0 . 9)mmHg。eNOS基因治疗 5d后 ,PP对NE的反应性显著低于对照组 (P <0 .0 1 ) ,其PP峰值为 (1 9. 9± 1 .0 )mmHg ;加入L NMMA后PP峰值虽升至 (2 3.5± 2 .0 )mmHg,但仍显著低于对照组PP(P <0 0 1 )。 (2 )活体门静脉注射L NMMA后 ,eNOS治疗组PVP虽由 (1 3. 9±0 . 7)mmHg升至 (1 9. 3± 1 . 0 )mmHg ,但仍显著低于对照组PVP(P <0 .0 1 ) ,活体试验与原位灌注结果相符。

Objective To evaluate the effects of endothelial nitric oxide synthase (eNOS) gene transfer on intrahepatic vascular resistance (IHVR) and portal venous pressure (PVP) in cirrhotic rats. Methods (1) 5 days after eNOS gene transfer, the in situ liver perfusion system (ISLP) was prepared and in different groups of controls and eNOS treated rats, the followings were analyzed: portal perfusion pressure (PP) dose-response curve to norepinephrine (NE); the effects on PP caused by specific nitric oxide synthase (NOS) inhibitor N-monomethyl-L- arginine (L-NMMA) or the nitric oxide (NO) synthesis substrate L-arginine (L-Arg). (2) The experiment of perfusion via portal vein in vivo was performed and the effects of L-NMMA on the PVP was observed. Results (1) In ISLP model, after L-NMMA was added into the perfusate of the control rats, PP dose-respose to NE increased remarkably and the peak of PP increased to (26.7±0.9) mm?Hg. The increased PP response to NE caused by L-NMMA was offsetted by L-Arg and the peak of PP decreased to (23.2±0.9) mm?Hg. In eNOS treated rats, PP response to NE was significantly lower than that in controls (P<0.01) and peak PP was (19.9±1.0) mm?Hg. When L-NMMA was added to the perfusate, peak PP in eNOS treated rats increased to (23.5± 2.0) mm?Hg which was still lower than in controls (P<0.01). (2) The experiment of perfusion via portal vein demonstrated that L-NMMA increased the PVP significantly in both of eNOS treated and controlled rats, but peak PVP was (19.3±1.0)mm?Hg in eNOS treated group which was lower than in controls (P<0.01). Conclusion eNOS gene transfer decreases the IHVR and PVP in cirrhotic rats.