不同剂量氯沙坦治疗大鼠肝硬化门静脉高压症的实验研究

Effect of different doses of losartan on portal hypertension in rats

目的探讨不同剂量氯沙坦对肝硬化门静脉高压症大鼠的治疗作用。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,43只雄性Wistar大鼠随机分为5组:正常对照组(n=7)、模型对照组(n=6)、三个治疗组分别给予10mg/(kg.d)、5mg/(kg.d)、2.5mg/(kg.d)高、中、低三种剂量氯沙坦(各组n=10)。结果治疗15d结束后,与模型对照组比较,各治疗组肝静脉压力梯度(HVPG)均有显著下降(P<0.05),但仍高于正常对照组(P<0.05)。治疗组之间比较差别无统计学意义。而高剂量组平均动脉压(MAP)从(94.44±11.23)mmHg下降到(70.81±12.57)mmHg。治疗组均可降低血清透明质酸(HA)的含量(P<0.05)。结论氯沙坦能有效地降低HVPG,减轻肝纤维化而用于门静脉高压症的治疗。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 investigate the effects of different doses of losartan on portal hypertension in rats. Methods Portal hypertension（PHT） models were induced by compound factors. A total of 43 rats were randomly divided into five groups： control group （n = 7） ,model group（ n = 6）, three treatment groups（ n = 10 in each group）. The rats in treatment groups were given different doses of losartan[10 mg/（kg·d）, 5 mg/（kg·d）, 2.5 mg/（kg·d）,respectively]. Results Compared with model group, hepatic venous pressure gradient（HVPG） in treatment groups significantly decreased after 15 d treatment（ P 〈 0.05）, but it was still higher than in control group（P 〈 0.05 ）. There was no significant difference between three treatment groups. However, mean arterial pressure（MAP） decreased from （94.44 ± 11.23）mmHg to （70.81 ± 12.57）mmHg in high dose treatment group. Compared with model group, the level of serum HA significantly decreased in three treatment groups （P 〈 0.05）. Conclusion Losartan can effectively decrease HVPG. And medium and low doses of losartan have the same effect, but have less influence on systemic hemodynamics.