Elliot A J, Vo L T, Grossman V L, Bhathal P S, Grossman H J
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
J Gastroenterol Hepatol. 1997 Apr;12(4):314-8. doi: 10.1111/j.1440-1746.1997.tb00427.x.
Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon tetrachloride-induced cirrhosis and normal controls, were used to investigate responses to the vasoactive peptide endothelin-1 (ET-1). The mean perfusion resistance (R) of cirrhotic IPRL was significantly greater than that of controls (2.63 +/- 0.24 vs 1.54 +/- 0.14 mmHg/mL per min per g; P < 0.01). Both control and cirrhotic IPRL demonstrated a concentration-related increase in resistance (delta R) in response to ET-1, with a minimum effective concentration of approximately 3 x 10(-11) mol/L. The EC50 (-log of the 50% effective concentration) was not significantly different between cirrhotic and control IPRL (8.48 +/- 0.19 and 8.79 +/- 0.11, respectively); however, the maximum response to ET-1 was significantly greater in cirrhotic preparations (R: 10.4 +/- 2.2 vs 4.4 +/- 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 +/- 2.1 vs 2.8 +/- 0.4 mmHg/mL per min per g, P < 0.01). Following maximal stimulation by ET-1, the mean portal-hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g was approximately 90% greater across cirrhotic IPRL than that across normal IPRL (11.2 +/- 2.0 vs 5.9 +/- 0.9 mmHg, respectively; P < 0.05). These results support the hypothesis that endogenously released ET-1 has a significant influence on the portal vascular resistance of cirrhotic liver in vivo and has an important role in the pathogenesis of portal hypertension.
从四氯化碳诱导的肝硬化大鼠和正常对照大鼠获得的离体灌注大鼠肝脏制剂（IPRL），用于研究对血管活性肽内皮素-1（ET-1）的反应。肝硬化IPRL的平均灌注阻力（R）显著高于对照组（2.63±0.24 vs 1.54±0.14 mmHg/mL每分钟每克；P<0.01）。对照和肝硬化IPRL对ET-1的反应均表现出浓度相关的阻力增加（ΔR），最小有效浓度约为3×10⁻¹¹ mol/L。肝硬化和对照IPRL的半数有效浓度（EC50，50%有效浓度的负对数）无显著差异（分别为8.48±0.19和8.79±0.11）；然而，肝硬化制剂对ET-1的最大反应显著更大（R：10.4±2.2 vs 4.4±0.5 mmHg/mL每分钟每克，P<0.01；ΔR，7.8±2.1 vs 2.8±0.4 mmHg/mL每分钟每克，P<0.01）。在ET-1最大刺激后，生理流速为1 mL/min每克时，肝硬化IPRL的平均门静脉-肝静脉压力梯度比正常IPRL大约高90%（分别为11.2±2.0 vs 5.9±0.9 mmHg；P<0.05）。这些结果支持以下假说：内源性释放的ET-1对体内肝硬化肝脏的门静脉血管阻力有显著影响，并且在门静脉高压的发病机制中起重要作用。
