Hryciw Deanne H, McAinch Andrew J
aDepartment of Physiology, The University of Melbourne bCentre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
Curr Opin Nephrol Hypertens. 2016 Sep;25(5):459-64. doi: 10.1097/MNH.0000000000000249.
The endocannabinoid system modulates cell signaling targets that are essential for energy homeostasis. Endocannabinoids bind to G protein-coupled receptors in the central nervous system and periphery, including the kidney. Modulation of cannabinoid receptor 1 (CB1) and CB2 activity in the kidney in diabetes and obesity has been identified as potential therapeutic target to reduce albuminuria and renal fibrosis. This review will highlight the results of recent studies that have identified a role for CB1 and CB2 in normal and pathological renal conditions.
CB1 and CB2 have been reported to play key roles in renal function and dysfunction. Recent studies have determined that antagonism of CB1 and agonism of CB2 in diabetic nephropathy and obesity associated kidney disease can reduce albuminuria, potentially by acting on both the glomeruli and tubules. Emerging studies have also identified a role for CB1 in renal diseases associated with fibrosis, with CB1 upregulated in multiple models of human nephropathies.
Emerging studies using isolated cells, rodent models, and human studies have identified a critical role for the endocannabinoid system in renal function and disease. Thus, therapeutics that modulate the activity of CB1 and CB2 in renal disease could become clinically relevant.
内源性大麻素系统调节对能量稳态至关重要的细胞信号靶点。内源性大麻素与中枢神经系统及外周（包括肾脏）中的G蛋白偶联受体结合。在糖尿病和肥胖症中，调节肾脏中大麻素受体1（CB1）和CB2的活性已被确定为减少蛋白尿和肾纤维化的潜在治疗靶点。本综述将重点介绍最近的研究结果，这些研究确定了CB1和CB2在正常和病理肾脏状况中的作用。
据报道，CB1和CB2在肾功能和功能障碍中起关键作用。最近的研究已确定，在糖尿病肾病和肥胖相关肾病中，拮抗CB1和激动CB2可能通过作用于肾小球和肾小管来减少蛋白尿。新出现的研究还确定了CB1在与纤维化相关的肾脏疾病中的作用，在多种人类肾病模型中CB1表达上调。
使用分离细胞、啮齿动物模型和人体研究的新出现的研究已确定内源性大麻素系统在肾功能和疾病中起关键作用。因此，调节肾脏疾病中CB1和CB2活性的疗法可能具有临床意义。
