Francois Helene, Lecru Lola
Inserm UMR_S 1155 Des Maladies Renales Rares Aux Maladies Frequentes, Remodelage et Reparation, France.
AP-HP, Service de Medecine Interne et Immunologie Clinique, Hopital Bicetre, 94270 Le Kremlin- Bicetre, France.
Curr Med Chem. 2018;25(7):793-801. doi: 10.2174/0929867324666170911170020.
Chronic kidney disease (CKD) remains a major challenge for Public Health systems and corresponds to the replacement of renal functional tissue by extra-cellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for CKD except nephroprotective strategies. The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in CKD.
We performed PubMed searches using the terms "cannabinoid receptors" in combination with "kidney" or "renal disease" or "nephropathy" or "diabetes" or "renal fibrosis" or "cellular pathways" in various combinations. We analyzed full-text English-language papers. We also searched the reference lists of identified articles for further relevant papers.
We gathered data regarding the current state of knowledge on the cannabinoid system in normal renal physiology and in various experimental nephropathies, especially diabetes. We also reviewed data obtained in models of diabetes and obesity as well as in non metabolic models of renal fibrosis when CB1 blockers and/or CB2 agonists were used. We also found that very few data are available so far regarding the cellular pathways involved downstream of the cannabinoid receptors in the development of renal fibrosis.
Overall, we found that the cannabinoid receptors are a promising target in the development of renal disease and fibrosis, particularly in CKD and diabetes.
慢性肾脏病（CKD）仍然是公共卫生系统面临的一项重大挑战，它表现为肾功能组织被细胞外基质蛋白（如胶原蛋白和纤连蛋白）所取代。迄今为止，除了肾脏保护策略外，尚无针对CKD的有效治疗方法。大麻素系统，尤其是大麻素受体1（CB1）和2（CB2），可能代表了CKD的一个新治疗靶点。
我们在PubMed上进行检索，使用了“大麻素受体”与“肾脏”或“肾脏疾病”或“肾病”或“糖尿病”或“肾纤维化”或“细胞信号通路”等术语的各种组合。我们分析了英文全文论文。我们还在已识别文章的参考文献列表中搜索了更多相关论文。
我们收集了关于正常肾脏生理学以及各种实验性肾病（尤其是糖尿病）中大麻素系统的现有知识状态的数据。我们还回顾了在糖尿病和肥胖模型以及使用CB1阻滞剂和/或CB2激动剂的肾纤维化非代谢模型中获得的数据。我们还发现，到目前为止，关于大麻素受体下游参与肾纤维化发展的细胞信号通路的数据非常少。
总体而言，我们发现大麻素受体是肾脏疾病和纤维化发展中的一个有前景的靶点，特别是在CKD和糖尿病中。
