氯沙坦对肝硬化门静脉高压症大鼠肝静脉压力梯度的影响

Effects of Losartan on HVPG in rats with portal hypertension

目的:探讨氯沙坦对肝静脉压力梯度(HVPG)的作用及其机制。方法:采用复合因素法制作大鼠肝硬化门静脉高压症(PHT)模型,49只雄性Wistar大鼠随机分为5组:正常对照组、模型对照组、3个治疗组(分别给予10mg.kg-1.d-1、5mg.kg-1.d-1、2.5mg.kg-1.d-13种剂量氯沙坦)。治疗21天结束后,进行各项指标检测。结果:①与正常对照组比较,模型对照组肝静脉楔入压(WHVP)、HVPG显著升高(P<0.05),游离肝静脉压(FHVP)、平均动脉压(MAP)和心率(HR)无明显变化;内皮型-氧化氮合酶(eNOS)的表达减少,肝匀浆氧化氮(NO)水平无明显变化但内皮素(ET)水平升高(P<0.05);②治疗21天结束后,与模型对照组比较,各治疗组HVPG均有显著下降(P<0.05),3组之间比较差别无统计学意义。而高剂量组导致了MAP的显著下降(P<0.05);③与模型对照组比较,各治疗组eNOS的表达显著升高(P<0.05),肝内NO含量增加而ET水平降低(P<0.05),各治疗组之间比较差别无统计学意义。结论:氯沙坦能有效地降低肝硬化大鼠的HVPG,中、低剂量具有与高剂量类似的治疗效果,且对全身血流动力学影响小。

Objective： To evaluate the effects and study the mechanisms of Losartan in rats with portal hypertension. Methods： Portal hypertension （PHT） model were induced by compound factors. PHT rats were randomly divided into one model group and three treatment groups. The treatment groups were given different doses of Losartan respectively （ 10mg · kg^-1· d^-1 , 5mg · kg^-1 · d^-1 and 2. 5mg · kg^-1· d^-1 ） . After treatment, hemodynamics and blood serum biochemistry index were measured. Results： （1）Compared with normal group, WHVP （ wedge hepatic vein pressure） and HVPG （ hepatic venous pressure gradient） of model group were significantly increased （ P 〈 0.05 ）, but FHVP （ Free hepatic venous pressure） , MAP （Mear arterial pressure） and HR （Heart rate） had no change. The level of eNOS was significantly decreased in model group, hepatic homogenate NO were normal between the normal and the model group but the level of ET was significantly increased （P 〈 0. 05 ） in model group. （2）Compared with model group, HVPG were significantly decreased in different doses of Losartan groups, but still higher than normal group. There weren＇t difference among the three treatment groups. However, the high dose group of Losartan had MAP decreased from （94. 44 ±11.23） mmHg to （70. 81 ± 12. 57） mmHg. （3）Compared with model group, the treatment groups had increased （ P 〈 0. 05 ） in the level of liver tissue eNOS and hepatic homogenate NO. And at the same time the level of ET were decreased significantly no matter what doses of Losartan were given. Conclusion： Losartan can decrease HVPG effectively, medium and low doses of Losartan have the same effect with high dose and make little influence to systemic hemodynamics.