哌唑秦、育亨宾和硝苯吡啶对肝硬变门脉高压鼠门静脉的作用

Effect of prazosin, yohimbine and nifedipine in portal vein of rats with liver cirrhosis and portal hypertension

目的探讨α肾上腺素受体亚型拮抗剂和钙通道阻滞剂对门静脉的作用机制及其在肝硬变门脉高压情况下的变化．方法采用药物受体分析技术，结合离体和整体实验，进行肝硬变门脉高压鼠和正常鼠的对照研究．分析测定了：①哌唑秦（ｐｒａｚｏｓｉｎｅ，Ｐｒａ），育亨宾（ｙｏｈｉｍｂｉｎｅ，Ｙｏｈ），硝苯吡啶（ｎｉｆｒｄｉｐｉｎｅ，Ｎｉｆ）与门静脉α受体的亲和力，②Ｐｒａ，Ｙｏｈ，Ｎｉｆ对门静脉收缩效应的影响；Ｐｒａ和Ｎｉｆ对门静脉压力的影响．结果正常鼠门静脉对Ｐｒａ的亲和力为Ｙｏｈ１２８倍，而ＰＨＴ鼠二者却相差不显著（Ｐ＞００５），其中对Ｐｒａ的亲和力下降了５倍，Ｙｏｈ增加了２７７倍．对Ｎｉｆ的亲和力正常鼠为ＰＨＴ鼠的１４倍．Ｐｒａ和Ｎｉｆ使门静脉收缩曲线显著右移，对门静脉收缩效应的抑制率分别为：对照组，Ｐｒａ７１２％，Ｎｉｆ８９９％，ＰＨＴ组，Ｐｒａ６８２％，Ｎｉｆ７４４％．Ｐｒａ能显著降低两组鼠的门静脉压力，Ｎｉｆ显著降低正常鼠的门静脉的压力，而ＰＨＴ鼠仅轻度下降（Ｐ＞００５）．结论门静脉突触后α受体亚型是α１，而α１的亚型主要是α１ａ，Ｐｒａ和Ｎｉｆ通过阻断α１和α１ａ受体而抑制门静脉收缩，降低门静脉压力．因此α?

IM Abstract:To investigate the mechanism of prazosin (Pra), yohimbine (Yoh) and nifedipine (Nif) in inhibiting the contraction of portal vein and decreasing the portal venous pressure (PVP).METHODS SD rats were divided into two groups randomly: control group (n=14) and PHT group (n=16, the model of rats with liver cirrhosis and portal hypertension were induced by thioacetamide). According to the effect in vivo and in vitro after antagonist treatment, the PA2, NE dose response effects of preparations, antagonist dissociation constant and PVP were evaluated using pharmacological methods.RESULTS The order of suppression of the maximal contraction in control group was Nif (899%)>Pra(712%)>Yoh(245%), and Nif (744%)>Pra(682%)>Yoh(267%) in PHT group. The order of PA2 in control group was Pra>Yoh>Nif and Yoh>Pra>Nif in PHT group. Pra decreased significantly the PVP in two groups (P<005), Nif reduced the PVP in control group (P<001), but it did not in PHT group (P>005).CONCLUSION In rat portal vein, the α adrenoceptor subtypes is α1 and α1a. Pra and Nif antagonize them to inhibit the contraction of portal vein and lower the PVP in PHT group. If the potency of α1 adrenoceptor is reduced, it would affect its value of clinical application.