长效奥曲肽对大鼠肝纤维化门静脉高压形成的影响

Effect of long-acting octreotide on portal hypertension in rats with liver fibrosis

目的:探讨长效奥曲肽对四氯化碳(CCl4)诱发大鼠肝纤维化门静脉高压的影响和机制.方法:SD大鼠40只,随机分为正常对照组(n=8)、肝纤维化门脉高压组(n=16)和长效奥曲肽组(n=16).以400mL/LCCl4sc(3mL/kg)建立大鼠肝纤维化门脉高压症模型,长效奥曲肽组同时给以长效奥曲肽(0.8mg/kg),每4wk肌肉注射1次.8wk后检测门静脉压力、肝脏组织形态学改变、血浆胰高血糖素和内皮素等.结果:长效奥曲肽组门静脉压、胰高血糖素和内皮素较肝纤维化门脉高压组显著降低(t=2.5,P<0.05;t=2.088,P<0.05;t=2.102,P<0.05),但仍高于正常对照组(t=5.152,P<0.01;t=2.896,P<0.01;t=2.770,P<0.05).正常对照组大鼠肝脏大体形态和组织学无异常改变;肝纤维化门脉高压组及长效奥曲肽组大鼠肝脏组织形态学表现为肝纤维化改变,但后者的病理损害指标显著轻于前者(P<0.05).结论:长效奥曲肽组大鼠门静脉压力显著低于肝纤维化门脉高压组,其机制可能与肝脏组织损害减轻、血浆胰高血糖素和内皮素降低等有关.

AIM： To observe the effect of long-acting release octreotide （Sandostatin LAR） on the genesis of portal hypertension in rats with liver fibrosis induced by carbon tetrachloride （CCl4）. METHODS： Forty SD rats were assigned randomly into 3 groups： normal control group （n = 8）, fibrosis with portal hypertension group （n = 16） and Sandostatin LAR group （n = 16）. Except those in the normal control group, the rats in the remaining two groups were subcutaneously injected with 400 mL/L CCl4 （3 mL/kg） for induction of fibrosis with portal hypertension. Sandostatin LAR （0.8 mg/kg） was used intramuscularly once every 4 weeks. After 8 weeks, the pressures of portal vein were measured before pathological evaluation including macroscopic features of the liver, and plasma glucagon as well as endothelin was determined by radioimrnunoassay. RESULTS： The portal pressure, plasma glucagon and endothelin levels were significantly lower in the Sandostatin LAR group than those in the fibrosis with portal hypertension group （t = 2.5, P 〈 0.05; t = 2.088, P 〈 0.05; t = 2.102, P 〈 0.05）, but still higher than those in the normal control group （t = 5.152, P 〈 0.01; t = 2.896, P 〈 0.01; t = 2.770, P 〈 0.05）. In the normal control group, liver morphology and histology were had no abnormal changes; in the fibrosis with portal hypertension group and Sandostatin LAR group, fibrotic changes were observed, and moreover, the severity was higher in the former group （P 〈 0.05）. CONCLUSION： Long-acting octreotide can remarkably decrease the pressures of portal vein, which may be attributed to reduced liver fibrosis and decreased plasma glucagon and endothelin levels.