门脉高压鼠血浆前列环素过多产生机制的实验研究

Mechanism of Overproduction of Plasma Prostacyclin in Portal Hypertensive Rats

探讨门脉压力升高和门体分流在前列环素(PGI_2)升高中的作用。方法:36只雄性SD大鼠随机分为4组:肝前型(PHPH,n=8)和肝内型门脉高压(IHPH,n=9)、端侧门腔分流(PCS,n=8)以及手术对照组(SO,n=11)。模型制备后两周:(1)测游离门脉压(FPP);(2)应用同位素微球技术研究全身及内脏血流动力学;(3)从股动脉采集血样,用放射免疫法测血浆6-酮-前列腺素F_1α(6-keto-PGF_1α)浓度。结果:心脏指数(CI)和内脏血流量(PVI)是PCS>PHPH>IHPH>SO鼠。门体分流率(PSS)是PCS>PHPH>IHPH。在PHPH、IHPH、PCS和SO鼠,血浆6-keto-PGF_1α的浓度(ng/ml)分别为6.93±2.43、5.09±2.27、2.36±1.01和1.56±0.61,前3组鼠均显著高于SO鼠(P<0.05),且PHPH鼠和IHPH鼠均显著高于PCS鼠(P<0.05)。血浆6-keto-PGF1_1α浓度与FPP值呈非常显著性正相关(r=0.67,P<0.001)。结论:在门脉高压中,PGI_2升高主要是门脉压力升高刺激其在血管内皮细胞的合成增加,而门体分流和肝功能减退起次要作用。此外,本研究结果并不支持PGI_2参与门脉高压高血流动力学的发生。

Aims:To evaluate the role of increased portal pressure and portosystemic shunting in elevated level of prostacyclin(PGI2) in portal hypertension. Methods: Thirty-six male Sprague-Dawley rats were divided into four groups: prehepatic portal hypertension(PHPH, n=8), intrahapetic portal hypertension(IHPH, n=9), end-to-side portacaval shunt(PCS, n = 8) and sham-operated controls(SO, n=ll). Two weeks after surgery, free portal pressure was measured; systemic and splanchnic hemodynamics was studied by radioactive microsphere technique and the level of plasma 6-keto-PGF1** with radio-immunoassay was measured in arterious blood. Results: Cardiac index(CI) and portal venous inflow(PVI) were in the order of PCS>PHPH>IHIH>SO rats. Portosystemic shunting(PSS) were PCS>PHPH>IHPH. The concentrations of plasma 6-keto-PGF1**(ng/ml) in PHPH, IHPH, PCS and SO rats were 6.93**2.43, 5.09 ** 2.27, 2.36**?.01 and 1.56 ** 0.61, respectively. The concentrations of plasma PGI2 in PHPH,IHPH and PCS rats were significantly higher than that in SO rats. Besides, the concentrations in PHPH and IHPH rats were also significantly higher than that in PCS rats. Moreover, a close positive correlation existed between plasma PGI2 and FPP(r=0.67, P<0.01). Conclusions: It is suggested that the elevated PIG2 in portal hypertension is mainly due to the overproduction of PGI2 in vascular epithelium cells induced by increased portal pressure, and portosystemic shunting and liver dysfunction play a secondary role. In addition, It's do not support that PIG2 mediates the hyperhemodynamics in protal hypertension.