The endocannabinoid system and liver diseases
The endocannabinoid system and liver diseases
复制标题
DOI：
10.1111/j.1365-2826.2008.01679.x
复制
发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Bernardi, M.
中科院分区：
文献类型：
--
作者：
Caraceni, P.;Domenicali, M.;Bernardi, M.
内源性大麻素（EC）是由许多中枢和外周作用提供的普遍存在的脂质信号分子，这些作用主要由特异性大麻素受体CB 1和CB 2介导。虽然这些受体的表达在健康肝脏中非常低甚至不存在，但相当多的一系列实验研究和一些临床观察已经认识到EC系统在肝脏疾病的病理生理学中是一个重要的参与者。EC系统在慢性肝病期间高度上调，并且迄今为止，它已涉及非酒精性脂肪性肝病的发病机制、纤维化向肝硬化的进展以及肝硬化的心血管异常的发展，例如高动力循环综合征和动脉硬化性心肌病。此外，EC系统影响负责急性肝损伤期间的细胞损伤和炎症反应的机制，例如由缺血-再灌注引起的机制。因此，靶向CB 1和CB 2受体的分子可能代表用于治疗肝脏疾病的潜在治疗剂。目前，CB 1拮抗剂代表了解决非酒精性脂肪性肝病患者脂肪蓄积和治疗肝硬化患者的最有吸引力的药物工具，因为它们可以减缓纤维化的进展并减弱与疾病晚期相关的心血管改变。
Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules provided by a number of central and peripheral effects, which are mainly mediated by the specific cannabinoid receptors CB1 and CB2. Although the expression of these receptors is very low or even absent in the healthy liver, a considerable series of experimental studies and some clinical observations have recognised the EC system as an important player in the pathophysiology of liver diseases. The EC system is highly up-regulated during chronic liver diseases and, to date, it has been implicated in the pathogenesis of non-alcoholic fatty liver disease, progression of fibrosis to cirrhosis and the development of the cardiovascular abnormalities of cirrhosis, such as the hyperdynamic circulatory syndrome and cirrhotic cardiomiopathy. Furthermore, the EC system influences the mechanisms responsible for cell damage and the inflammatory response during acute liver injury, such as that resulting from ischaemia-reperfusion. Thus, molecules targeting the CB1 and CB2 receptors may represent potential therapeutic agents for the treatment of liver diseases. At present, the CB1 antagonists represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non-alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.