不同剂量依贝沙坦治疗大鼠门静脉高压症的实验研究

Effect of different doses of irbesartan on portal hypertension in cirrhotic rats

目的探讨不同剂量依贝沙坦对大鼠门静脉高压症的治疗作用及副作用。方法成年雄性Wistar大鼠门静脉高压形成后,随机分为4组,即模型组、高[13.6 mg/(kg.d)]、中[6.8 mg/(kg.d)]、低[3.4 mg/(kg.d)]剂量治疗组,每组7只,另取8只正常大鼠为正常对照组。治疗14 d,分别从肝静脉、颈动脉插管测量肝静脉压力梯度(HVPG)、平均动脉压(MAP)。结果与模型组相比,各治疗组HVPG均有显著下降(P<0.05),治疗组间差别无统计学意义,MAP高剂量组显著下降(P<0.05),中低剂量组与模型组无明显差别。结论依贝沙坦具有降低大鼠肝硬化门静脉压力的作用,中低剂量具有与高剂量类似的治疗效果,且对大鼠全身血流动力学影响较小。

Objective To assess the effects of different doses of irbesartan on portal hypertension in cirrhotic rats,and to evaluate its safety.Methods The adult male Wistar rats with portal hypertension were divided into 4 groups（n=7 each group）： model group without drug treatment and treated groups [treated with irbesartan 13.6 mg/（kg·d）,6.8 mg/（kg·d）,3.4 mg/（kg·d）,respectively].Eight normal rats served as controls.Hepatic venous pressure gradient（HVPG） and mean arterial pressure（MAP） were measured after treatment for 14 d.Results Compared with model group,HVPG decreased significantly in treated groups（P〈0.05）,but there was no significant difference between treated groups.The fall in MAP was significantly higher in high dose treated group than in low dose groups（P〈0.05）. Conclusion Irbesartan could induce a moderate reduction in portal pressure.High dose of irbesartan would cause hypotension,but low doses could reduce portal hypertension without hypotensive side-effects.