Bhathal P S, Grossman H J
J Hepatol. 1985;1(4):325-37. doi: 10.1016/s0168-8278(85)80770-4.
This study was undertaken to compare the in vitro responses of the portal vascular bed of normal and cirrhotic rat livers to a variety of vasodilator agents. Using carbon tetrachloride-induced cirrhosis in the rat as a model, isolated liver preparations were perfused via the portal vein with a synthetic medium (2.5% bovine serum albumin in Krebs-Henseleit buffer) to eliminate extrahepatic neural and humoral influences. Under these experimental conditions the mean perfusion resistance of the cirrhotic livers was approximately 117% higher than in controls (P less than 0.001). The vascular tone of the normal liver was minimal as assessed by the response to a variety of vasodilator agents, including sodium nitroprusside (3.0 X 10(-3) M), magnesium sulphate (6.0 X 10(-2) M), papaverine hydrochloride (6.4 X 10(-4) M), and cytochalasin B (6.3 X 10(-5) M). In contrast, these agents reduced the perfusion resistance of the cirrhotic livers by approximately 15%. Prostaglandin E1 (3.0 X 10(-6) M) and isoprenaline hydrochloride (2.4 X 10(-6) M) produced a lesser fall in resistance which nevertheless was greater in cirrhotic livers than controls. Cirrhotic livers, unlike the controls, were found to contain large numbers of myofibroblasts in perivenous and perisinusoidal locations. Previous studies have shown that myofibroblasts are capable of sustaining a high level of intrinsic tone and relax in response to vasodilator agents. It is concluded that part of the increased resistance to flow through the portal vascular bed of the cirrhotic rat liver in vitro is due to an increase in intrinsic vascular tone, possibly mediated via myofibroblasts, and can be reversed by pharmacological agents.
本研究旨在比较正常和肝硬化大鼠肝脏门静脉血管床对多种血管扩张剂的体外反应。以四氯化碳诱导的大鼠肝硬化作为模型，通过门静脉用合成培养基（克雷布斯 - 亨斯莱特缓冲液中含2.5%牛血清白蛋白）灌注分离的肝脏制剂，以消除肝外神经和体液的影响。在这些实验条件下，肝硬化肝脏的平均灌注阻力比对照组高约117%（P小于0.001）。通过对多种血管扩张剂的反应评估，正常肝脏的血管张力最小，这些血管扩张剂包括硝普钠（3.0×10⁻³M）、硫酸镁（6.0×10⁻²M）、盐酸罂粟碱（6.4×10⁻⁴M）和细胞松弛素B（6.3×10⁻⁵M）。相比之下，这些药物使肝硬化肝脏的灌注阻力降低了约15%。前列腺素E1（3.0×10⁻⁶M）和盐酸异丙肾上腺素（2.4×10⁻⁶M）使阻力下降幅度较小，但在肝硬化肝脏中仍比对照组大。与对照组不同，发现肝硬化肝脏在静脉周围和窦周部位含有大量肌成纤维细胞。先前的研究表明，肌成纤维细胞能够维持高水平的内在张力，并对血管扩张剂产生松弛反应。得出结论，体外肝硬化大鼠肝脏门静脉血管床血流阻力增加的部分原因是内在血管张力增加，可能通过肌成纤维细胞介导，并且可以被药物逆转。
