Faramarzi Negar, Abbasi Ata, Tavangar Seyed M, Mazouchi Marjan, Dehpour Ahmad R
Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
J Gastroenterol Hepatol. 2009 Jul;24(7):1226-9. doi: 10.1111/j.1440-1746.2009.05794.x. Epub 2009 May 26.
Angiogenesis, formation of new capillaries from existing vasculature, plays a pivotal role in different pathological states such as many chronic inflammatory diseases including the chronic liver diseases. There is increasing evidence demonstrating accumulation of endogenous opioids and their role in the pathophysiology and manifestations of cholestasis, the main feature of a number of chronic progressive liver diseases. Hence, we investigated the significance of endogenous opioids in angiogenesis in an experimental model of cholestasis.
Cholestasis was induced in male Sprague-Dawley rats by bile duct ligation and resection. Naltrexone, an opioid antagonist (20 mg/kg/day) was administered to cholestatic animals for 22 +/- 1 days. The serial sections from liver tissue were stained with von Willebrand Factor antibody and micro-vessel density was assessed by calculating mean micro-vessel number in three hot spots high power microscopic fields.
Naltrexone treatment in bile duct ligated rats led to a marked increase in the micro-vessel number (6.34 +/- 0.21 vs 5.61 +/- 0.22) (P < 0.05), which had already increased during cholestasis.
In order to clarify the impacts of opioid system blockade in cirrhosis, our findings demonstrate the promoting role of opioid antagonist in angiogenesis in a rat model of cholestasis.
血管生成是指从现有脉管系统形成新的毛细血管，在多种病理状态中发挥关键作用，如包括慢性肝病在内的许多慢性炎症性疾病。越来越多的证据表明内源性阿片类物质的蓄积及其在胆汁淤积（多种慢性进行性肝病的主要特征）的病理生理学和表现中的作用。因此，我们在胆汁淤积的实验模型中研究了内源性阿片类物质在血管生成中的意义。
通过胆管结扎和切除在雄性Sprague-Dawley大鼠中诱导胆汁淤积。给胆汁淤积的动物注射阿片类拮抗剂纳曲酮（20mg/kg/天），持续22±1天。用血管性血友病因子抗体对肝组织的连续切片进行染色，并通过计算三个高倍显微镜视野热点中的平均微血管数量来评估微血管密度。
在胆管结扎的大鼠中，纳曲酮治疗导致微血管数量显著增加（6.34±0.21对5.61±0.22）（P<0.05），而微血管数量在胆汁淤积期间已经增加。
为了阐明阿片系统阻断在肝硬化中的影响，我们的研究结果表明阿片类拮抗剂在胆汁淤积大鼠模型的血管生成中具有促进作用。
