大麻素受体1对小鼠脂质代谢的作用研究
Effect of Cannabinoid Receptor 1 on Lipid Metabolism in Diet-induced Obese Mice

中文摘要： 目的 研究大麻素受体1（CB1）对高脂饮食诱导肥胖模型小鼠脂质代谢调节作用的机制。 方法 高脂饮食喂养雄性C57BL/6J小鼠构建肥胖模型小鼠。灌胃给药CB1抑制剂利莫那班（SR141716），观察小鼠体质量、肝脏质量及血清生化指标，检测CB1在皮下脂肪、内脏脂肪、骨骼肌、肝脏、心脏中的mRNA和蛋白质水平，着重探索CB1对肉碱棕榈酰转移酶1（ CPT1）基因在mRNA水平表达情况的变化。 结果 SR141716抑制了CB1在小鼠各组织中mRNA和蛋白质水平的表达（ P<0.05），显著降低了小鼠体质量、肝脏质量（ P<0.05），降低了血清总胆固醇、高密度脂蛋白、脂联素和瘦素含量（ P<0.05）；CB1受抑制后，组织中 CPT1A和 CPT1B基因mRNA的表达水平明显上调（ P<0.05）；未检测到 CPT1A和 CPT1B在心脏的差异表达。 结论 证实CB1通过作用于 CPT1A、 CPT1B基因发挥对脂质代谢的调节作用，为靶向调控脂质代谢提供了可靠的依据。
英文摘要： Objective To study the regulatory mechanism of cannabinoid receptor 1 (CB1) on the lipid metabolism of diet-induced obese mice. Methods The C57BL/6J male mice were feed with high-fat diet, and then the effect of rimonabant on the body mass, liver mass and serum biochemical index of mice were detected. In particular, the mRNA levels of CB1 and carnitine palmitoyltransterase-1( CPT1), and protein levels of CB1 in subcutaneous fat, visceral fat, skeletal muscle, liver and heart were also tested. Results It was showed the body mass and liver mass, as well as the mRNA and protein levels of CB1 were all significantly decreased in rimonabant-treated mice ( P<0.05). Simultaneously, the levels of total cholesterol, high density lipoprotein, adiponectin and leptin were improved ( P<0.05). Furthermore, the mRNA levels of carnitine palmitoyltransterase-1A ( CPT1A) and carnitine palmitoyltransterase-1B ( CPT1B) in each tissue were increased, while no obviously difference was detected in the expression of CPT1A and CPT1B in mouse heart. Conclusion It was suggested that CB1 can regulate lipid metabolism by controlling the expression of CPT1A and CPT1B genes. A basis for clinical treatment of lipid metabolism disorders was provided. 2018,37(1): 51-56 收稿日期：2017-05-22 DOI：10.11984/j.issn.1000-7083.20170165 分类号：Q95-33 基金项目：四川省教育厅基金项目（14ZA0146） 作者简介：魏立雯(1987-),女,硕士,主要从事实验动物学研究,E-mail:weilwen55@swmu.edu.cn *通讯作者：付陆,男,博士,主要从事分子生物学研究,E-mail:flfyh@swmu.edu.cn 参考文献： 胡予, 马慧, 诸骏仁. 2007. 利莫那班-从阻断大麻素受体到控制心血管代谢危险因素[J]. 中国实用内科杂志, 27(17):1405-1407. 马微, 付丽, 王海波, 等. 2010. 新型减肥药利莫那班的研究进展[J]. 黑龙江医药, 23(1):19-21. 汤劐菱, 王莉莉, 王莉, 等. 2007. 利莫那班减肥作用及机制研究进展[J]. 中国药理学通报, 23(7):844-847. 王瑾, 周炳杰, 耿骥, 等. 2016. 利莫那班衍生物对高脂肥胖模型小鼠的减肥作用[J]. 江苏大学学报(医学版), 26(2):119-123. Amengual J, Petrov P, Bonet ML, et al. 2012. Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells[J]. The International Journal of Biochemistry & Cell Biology, 44(11):2019-2027. Crespillo A, Suárez J, Bermúdez-silva FJ, et al. 2010. Expression of the cannabinoid system in muscle:effects of a high-fat diet and CB1