Mallat A, Lotersztajn S
Unite INSERM 581, Hopital Henri Mondor, 94010 Creteil, France.
J Endocrinol Invest. 2006;29(3 Suppl):58-65.
In the past two decades, cannabinoids have emerged as crucial mediators in a variety of pathophysiological conditions. Awareness of their critical functions in liver pathophysiology is only recent, probably given the low level of expression of cannabinoid receptor type 1 (CB1 receptor) and type 2 (CB2 receptor) in normal liver. However, it has been shown that non-alcoholic fatty liver disease and cirrhosis are associated to a marked upregulation of the hepatic endocannabinoid system, including increases in endocannabinoids and in hepatic CB receptors, both in humans and in rodents. Consequently, a growing number of cannabinoid-related hepatic effects are being unravelled. Hence, hepatic CB1 receptors enhance liver steatogenesis in a mouse model of high fat-induced obesity, and contribute to peripheral arterial vasodilation in cirrhosis, thereby promoting portal hypertension. In addition, CB1 and CB2 receptors elicit dual opposite effects on fibrogenesis associated to chronic liver injury, by promoting pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies may open novel therapeutic avenues in the treatment of chronic liver diseases.
在过去二十年中，大麻素已成为多种病理生理状况下的关键介质。人们对其在肝脏病理生理学中的关键作用的认识只是最近才有的，这可能是因为大麻素1型受体（CB1受体）和2型受体（CB2受体）在正常肝脏中的表达水平较低。然而，研究表明，非酒精性脂肪性肝病和肝硬化与肝脏内源性大麻素系统的显著上调有关，包括内源性大麻素和肝脏CB受体在人类和啮齿动物中的增加。因此，越来越多与大麻素相关的肝脏效应正在被揭示。因此，肝脏CB1受体在高脂肪诱导的肥胖小鼠模型中增强肝脏脂肪生成，并在肝硬化中促进外周动脉血管舒张，从而导致门静脉高压。此外，CB1和CB2受体分别通过促进促纤维化和抗纤维化作用，对与慢性肝损伤相关的纤维化产生双重相反的影响。因此，基于内源性大麻素的疗法可能为慢性肝病的治疗开辟新的治疗途径。
