目的 研究津力达颗粒对高脂饮食诱导的肥胖小鼠代谢紊乱及成纤维细胞生长因子21（fibroblast growth factor 21，FGF21）/磷酸腺苷活化蛋白激酶（AMP-dependent/activated protein kinase，AMPK）信号通路的影响。方法 C57BL/6J小鼠随机分为对照组、模型组、津力达颗粒（3.8 g/kg）组，对照组小鼠喂食标准饲料，其余各组小鼠喂食高脂饲料；给予津力达颗粒进行干预后，每周称定小鼠体质量并记录小鼠日摄食、饮水量；ELISA法检测各组小鼠血清中三酰甘油（triglycerides，TG）、总胆固醇（total cholesterol，TC）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）和高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平；苏木素-伊红（HE）染色法观察各组小鼠肝脏、脂肪组织病理变化；通过腹膜内葡萄糖耐量实验测定各组小鼠血糖水平；qRT-PCR和Western blotting法检测小鼠肝脏和脂肪组织中FGF21/AMPK通路相关基因和蛋白的表达。结果 与模型组比较，津力达颗粒组小鼠体质量、棕色脂肪质量、白色脂肪质量、肝脏质量显著降低（P<0.05、0.01、0.001）；血清TG、LDL-C水平显著降低（P<0.01、0.001），HDL-C水平显著升高（P<0.001）；血糖水平显著降低（P<0.01、0.001）；肝脏FGF21、成纤维生长因子受体1（fibroblast growth factor receptors 1，FGFR1）mRNA表达水平显著升高（P<0.05、0.01）；肝脏FGF21、p-AMPK、p-AMPK/AMPK蛋白表达水平明显升高（P<0.05、0.001），肝脏AMPK、Klotho、沉默信息调节因子1（silent information regulator 1，SIRT1）蛋白水平明显降低（P<0.05）；脂肪FGF21 mRNA表达水平显著升高（P<0.01），脂肪FGFR1、AMPK、p-AMPK蛋白表达水平明显升高（P<0.05、0.001）。结论 津力达颗粒可以通过调节FGF21及其蛋白受体复合物（FGFR1/β-Klotho），进一步激活AMPK信号通路，改善高脂饮食诱导的代谢紊乱，为津力达颗粒在代谢综合征的临床应用提供依据。

Objective To study the effect of Jinlida Granules (津力达颗粒) on metabolic disorder and FGF21/AMPK signaling pathway in obese mice induced by high fat diet. Methods C57BL/6J mice were randomly divided into control group, model group and Jinlida Granules (3.8 g/kg) group, mice in control group were fed with standard diet, and mice in the other groups were fed with high-fat diet. After intervention with Jinlida Granules, the mice were weighed weekly, and the daily intake and drinking water of mice were recorded; The levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) in serum of mice in each group were detected by ELISA; The pathological changes of liver and adipose tissue of mice in each group were observed by HE staining. The levels of blood glucose were measured by tolerance test, and the expressions of FGF21/AMPK pathway related genes and proteins in liver and adipose tissue were detected by qRT-PCR and Western blotting. Results Compared with model group, weight of body, brown fat, white fat and liver were significantly reduced in mice of Jinlida Granules group (P<0.05, 0.01, 0.001), serum TG and LDL-C levels were significantly reduced (P<0.01, 0.001), HDL-C level was significantly increased (P<0.001), blood glucose level was significantly reduced (P<0.01, 0.001), the mRNA levels of FGF21 and FGFR1 in liver were significantly up-regulated in Jinlida Granules group (P<0.05, 0.01), the protein expressions of FGF21, p-AMPK and p-AMPK/AMPK in liver of Jinlida Granules group were significantly up-regulated (P<0.05, 0.001), the protein expressions of AMPK, Klotho, and SIRT1 in liver were significantly down-regulated (P<0.05), the mRNA level of FGF21 in fat was significantly up-regulated (P<0.01), the protein expressions of FGFR1, AMPK and p-AMPK in fat were significantly up-regulated (P<0.05, 0.001). Conclusion Jinlida Granules can further activate AMPK signaling pathway by regulating FGF21 and its protein receptor complex (FGFR1/β-Klotho), further improve the metabolic disorder induced by high-fat diet, which provide the basis for the clinical application of Jinlida Granules in metabolic syndrome.

R285.5

国家重点研发计划重点专项资助项目（2017YFC1700501）；京津冀基础研究合作重大项目（H2019106062）；河北省重点研发计划项目（18277763D）；河北省中医药管理局科研计划课题（2018200）；北京市科技计划课题（Z181100001918015）