肾上腺髓质素对肝硬化大鼠门静脉压力的影响

Effects of Adrenomedullin on Portal Vein Pressure in Cirrhotic Rats

【目的】了解肝硬化时大鼠肾上腺髓质素 (ADM )浓度是否改变 ;探讨外源性ADM(1 52 ) 对肝硬化大鼠门静脉压力的影响。【方法】以四氯化碳 (CCl4)诱导肝硬化大鼠模型 ,测定大鼠血浆ADM浓度。以ADM(1 52 ) 3nmol/kg ,经股静脉注射 ,持续监测大鼠门静脉压力的变化。测定肝硬化大鼠门静脉压力降至最低时内皮素 1(ET 1)及一氧化氮 (NO)的浓度。【结果】肝硬化大鼠血浆ADM浓度明显高于正常大鼠 (P <0 .0 1)。经股静脉注射ADM(1 52 ) 可迅速导致肝硬化大鼠门静脉压力显著下降 (P <0 .0 1) ,约 3.5min时下降至最低 ;约 9min基本恢复原水平。而正常大鼠注射ADM(1 52 ) 后 ,门静脉压力下降不明显 (P >0 .0 5 )。在肝硬化大鼠门静脉压力降至最低时 ,大鼠ET 1及NO浓度较未用药时无明显改变 (P >0 .0 5 )。【结论】血浆ADM浓度在肝硬化时升高 ;外源性ADM(1 52 ) 可显著降低肝硬化大鼠门静脉压力 ,而对正常大鼠门静脉压力无明显影响。ADM可能不是通过影响ET 1和NO的产生而发挥其降压作用。

Objectives]To understand whether the plasma concentration of adrenomedullin (ADM) has changed in cirrhotic rats and explore the effects of exogenous ADM (1-52) on their portal vein pressure (PVP).Cirrhotic rat models were established by induction with carbon tetrachloride(CCl 4), their plasma concentration of ADM was estimated by radioimmunoassay(RIA). The changes of PVP were monitored persistently after administration with 3nmol/kg of ADM (1-52) through femoral vein. Plasma endothelin-1(ET-1) and serum nitrogen monoxide (NO) concentrations during the lowest level of PVP were measured by RIA and method of nitric acid reductase, respectively.Plasma concentration of ADM in cirrhotic rats was significantly higher than that in normal rats (P<0.01). Administration of ADM (1-52) through femoral vein could rapidly cause a prominent decrease of PVP in cirrhotic rats (P<0.01), reaching its lowest level in 3.5 min , and PVP essentially returned to its original level in 9 min after administration ; whereas obvious decline of PVP was not observed in normal rats after intravenous injection of ADM (1-52) (P>0.05). There were no distinct changes of both ET-1 and NO concentrations in cirrhotic rats when their PVP decreased to the lowest level as compared to those before ADM administration (P>0.05).[Conclusion]The plasma concentration of ADM is significantly increased in cirrhotic rats, exogenous ADM (1-52) can markedly decrease their PVP; whereas it shows no evident effect on normal rats. The hypotensive effects of ADM (1-52) may not be mediated by altering the production of ET-1 and NO.