目的 探究大麻二酚(cannabidiol,CBD)对高脂饮食老龄小鼠肝脏脂肪变性的保护作用及其信号机制。方法 30只老龄雄性C57BL/6J小鼠随机分为三组:正常饮食组 (NC组;基础饲料)、高脂饮食组(HFD组;高脂饲料)和CBD治疗组(CBD组;高脂饲料加大麻二酚治疗)。12周后,测定各组小鼠血清葡萄糖、三酰甘油(TG)、总胆固醇(TC)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)、胰岛素、游离脂肪酸(FFA)。葡萄糖耐量实验(IPGTT)和胰岛素耐量实验(ITT)检测小鼠糖处理能力。油红O染色检测小鼠肝脏的脂质沉积情况。qRT-PCR检测脂代谢相关基因的mRNA表达,Western blot检测腺苷酸激活蛋白激酶(AMPK)及乙酰辅酶A羧化酶(ACC)蛋白水平。结果 与NC组比较,HFD组小鼠的血糖、TG、TC、FFA、ALT及AST均显著升高,肝脏脂质沉积增加(P＜0.05)。CBD组的上述糖脂代谢相关指标明显降低(P＜0.05),小鼠对葡萄糖的处理能力提高,肝脏脂质沉积减轻,脂代谢相关基因的mRNA表达水平降低(P＜0.05)。CBD显著增加磷酸化AMPK及ACC的蛋白表达水平(P＜0.05)。结论 CBD能缓解高脂饮食老龄小鼠肝脏脂肪变性,AMPK/ACC信号通路可能参与了这一过程。
Abstract
Objective To explore the therapeutic effect and signaling mechanisms of cannabidiol (CBD) intervention on hepatic steatosis in aged mice fed with a high fat diet.Methods Thirty aged male C57BL/6J mice were randomly divided into three groups: normal diet group (NC), high-fat diet group (HFD) and cannabidiol intervention group (CBD). After intervention for 12 weeks, the serum levels of glucose,triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer, serum insulin level was detected by ELISA kit, and free fatty acid (FFA) level was determined by colorimetric analysis kit. Intraperitoneal glucose tolerance tests (IPGTT) and insulin tolerance test (ITT) were used to examine the glucose disposal ability. Lipid deposition in liver was detected by oil red O staining. The mRNA expression levels of lipid metabolism-related genes were evaluated by qRT-PCR. Western blot was used to detect the protein levels of AMPK and ACC.Results Compared with NC mice, the levels of blood glucose, TC, TG, FFA, ALT and AST in HFD mice significantly increased, and liver lipid deposition also increased (P<0.05). However, CBD intervention reduced the levels of parameters related to glucolipid metabolism (P<0.05), improved the ability of glucose disposal ability, alleviated lipid deposition in liver, and improved mRNA expression levels of lipid metabolism-related genes (P<0.05). Meanwhile, CBD significantly increased the protein expression levels of p-AMPK and p-ACC (P<0.05).Conclusion CBD alleviates hepatic steatosis in aged mice fed with a high fat diet, and AMPK/ACC signaling pathway may be involved in this progress.
关键词
大麻二酚 /
肝脂肪变性 /
AMPK/ACC通路
Key words
cannabidiol /
hepatic steatosis /
AMPK/ACC signaling pathway
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基金
中国博士后科学基金资助项目(2019T120977)
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