阿罗洛尔、普萘洛尔和卡维地洛对肝硬化大鼠门脉高压症的疗效比较

摘要

ABSTRACT:Objective To study the effects of arotinolol,propranolol and carvedilol on rat portal hypertension and make a comprehensive evaluation of the three drugs.Methods Portal hypertension was induced with CCl4 in rats.Arotinolol,propranolol,and carvedilol were administered for 2 weeks after the model was stable.Mean arterial pressure (MAP),heart rate (HR)and portal venous pressure (PVP)were measured at intubation;α-SMA expression was measured by immunohistochemistry;Masson staining was used to test collagen fibers area.Results Compared with model group,both arotinolol and carvedilol could significantly reduce PVP level (P <0.001),which was lower than that in propranolol group (P <0.001,P =0.032).Compared with those in model group,both MAP and HR in arotinolol group and carvedilol group were significantly reduced (P <0.05),MAP in carvedilol group was lower than in arotinolol group (P = 0.01 1 ).MAP was obviously decreased in propranolol group compared with model group (P =0.003),but HR had no sighificant difference between the two groups (P =0.143).Only TBIL in arotinolol and propranolol groups reduced significantly compared with model group (P <0.001 ).However,ALT, ALB and TBIL were obviously ameliorated in carvedilol group compared with model group (P <0.001,P <0.001, P =0.045).The expression ofα-SMA and the area of collagen fibers in arotinolol,carvedilol and propranolol groups significantly declined compared with those in model group (P <0.05 ).Conclusion Arotinolol can significantly reduce cirrhotic rats’ portal pressure,with effects similar to those of carvedilol.The effect of arotinolol in improving liver function is weaker than that of carvedilol,but the side effects on MAP are milder than those of carvedilol.%目的：探讨阿罗洛尔、普萘洛尔和卡维地洛降低肝硬化门脉高压症大鼠门静脉压力的疗效及相关机制,并对此3种药物的作用优劣作综合评估。方法CCl4诱导大鼠肝硬化门脉高压症模型,于模型稳定后分别给予阿罗洛尔、普萘洛尔、卡维地洛灌胃2周；插管法测平均动脉压(MAP)、心率(HR)及门静脉压力(PVP),免疫组织化学法测定肝组织中α-SMA 表达；Masson 染色法测胶原纤维面积。结果阿罗洛尔组和卡维地洛组 PVP 较模型组均显著降低,差异有统计学意义(P <0.001),且两组 PVP 均低于普萘洛尔组(P <0.001,P =0.032)；和模型组比较,阿罗洛尔组及卡维地洛组的 MAP 和 HR 均明显下降(P <0.05)；卡维地洛组 MAP 较阿罗洛尔组更低(P =0.011)；普萘洛尔组仅MAP 较模型组显著下降(P =0.003),而 HR 变化无统计学差异(P =0.143)。阿罗洛尔组和普萘洛尔组仅 TBIL 较模型组显著下降(P <0.001),而卡维地洛组 ALT、ALB、TBIL 均较模型组明显改善(P <0.001,P <0.001,P =0.045)；阿罗洛尔、卡维地洛、普萘洛尔组α-SMA 表达及胶原纤维面积均较模型组减少,差别有统计学意义(P <0.05)。结论阿罗洛尔能够显著降低肝硬化门脉高压症大鼠的门静脉压力,疗效与卡维地洛类似；在改善肝功能方面阿罗洛尔不及卡维地洛,但阿罗洛尔对 MAP 的影响要小于卡维地洛。