联合应用特利加压素和川芎嗪对门静脉高压大鼠的有益作用。

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats.

作者信息

Chang F C, Huang Y T, Lin H C, Hong C Y, Lin J G, Chen K J

机构信息

Xiyuan Hospital and Institute of Geriatrics, China Academy of Traditional Chinese Medicine, Beijing, China.

出版信息

Can J Physiol Pharmacol. 1999 Aug;77(8):618-24.

PMID:10543725

Abstract

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

摘要

本研究旨在探讨特利加压素（TP）单独或与川芎嗪（TMP）联合应用对麻醉的门静脉高压大鼠的治疗效果。通过在Sprague-Dawley大鼠中进行部分门静脉结扎（PVL，无肝硬化）或胆管结扎（BDL，有肝硬化）诱导门静脉高压。每只PVL或BDL大鼠仅接受两种治疗方案中的一种：先给予赋形剂3分钟，然后给予TP（0.017mg·kg⁻¹·min⁻¹，持续3分钟），或先给予TMP（10mg·kg⁻¹·min⁻¹，持续3分钟），然后给予TP。在PVL大鼠中，先输注赋形剂再给予TP可使门静脉压力（PVP）显著降低（-15.0±1.0%），平均动脉压（MAP）显著升高（57.3±8.1%），总外周阻力（TPR）较基线显著升高（113±11%），并且存在心脏抑制反应（心脏指数，CI，-26.3±1.1%）。先输注TMP再给予TP可使PVP显著降低（-20.3±0.4%），CI降低（-9.9±1.2%），MAP显著升高（31.3±2.5%），TPR升高（46.0±4.1%）。在BDL大鼠中，先输注赋形剂再给予TP也可使PVP显著降低（-13.8±1.7%），但MAP升高（57.1±2.2%），TPR升高（101±6%），并且也存在心脏抑制反应（CI，-21.4±2.3%）。先输注TMP再给予TP可使PVP显著降低（-18.9±1.4%），CI降低（-11.9±2.1%），但MAP升高（36.2±2.5%），TPR升高（55.0±5.2%）。与先给予赋形剂再给予TP相比，TMP不仅显著增强了TP的门静脉降压（降低PVP）作用，还减弱了TP在PVL和BDL大鼠中的全身升压（升高MAP和TPR）和心脏抑制（降低CI）作用。我们的结果表明，TP单独或与TMP联合应用在两种门静脉高压大鼠模型中均能诱导门静脉降压作用。TP与TMP联合应用有利于增强TP的门静脉降压作用，并改善TP的全身升压和心脏抑制作用。