探讨兰州百合对高脂喂养大鼠肝脏生物钟基因Clock-Bmal1及糖脂代谢的调节及作用机制。高脂饲料喂养大鼠8周造模，将其随机分为模型组、二甲双胍组、褪黑素组、百合低、中、高剂量组、联合组，正常组普通饲料喂养，灌胃干预4周，测量空腹血糖（FPG）、腹围、体长、肝重，计算Lee’s指数及肝脏湿重指数，微板法检测血清和肝脏总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）、ELISA法检测糖化血红蛋白（Hb Alc）水平，RT-qPCR和Western blot检测肝脏Clock、Bmal1基因mRNA及蛋白表达水平。结果显示，与模型组相比，百合干预组可改善高脂大鼠体态，调节血脂水平，降低Hb Alc，上调Clock和Bmal1 mRNA及蛋白表达（P<0.05），其中百合中剂量腹围及Lee’s指数减少（8.61%，5.04%），血清TC、TG、LDL-C下降（36.59%、29.73%、34.04%），Hb Alc下降24.37%，Clock和Bmal1 mRNA表达增加（159.17%、228.58%）以及蛋白表达增加（52.09%、151.33%）。综上，百合缓解高脂饮食引起的糖脂代谢紊乱，可能是通过增加肝脏Clock 和Bmal1基因表达来实现的，可为百合防治营养代谢性疾病及功能性健康食品的开发利用提供理论依据。

To explore the regulation and mechanism of Lilium davidii var. willmottiae (LD) on the liver circadian clock gene Clock-Bmal1 and glucose and lipid metabolism in rats on a high-fat diet. The model was established by feeding rats with high-fat diet for 8 weeks. The high-fat rats were randomly divided into the model group, metformin group, melatonin group, low-dose LD group, medium-dose LD group, high-dose LD group, combination group, with the normal group being fed with an ordinary diet. Intragastric intervention was carried out for 4 weeks. Fasting blood glucose (FPG), abdominal circumference, body length, and liver weight were measured. Lee's index and liver wet weight index were calculated. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) in the serum and liver were detected by the microplate method. The level of glycosylated hemoglobin (Hb Alc) was detected by ELISA. The mRNA and protein expression levels of the Clock and Bmal1 genes in the liver were detected by RT qPCR and Western blot. The results showed that compared with the model group, the LD intervention group could improve the body posture of high-fat rats, regulate the blood lipid levels, reduce Hb Alc, and upregulate the mRNA and protein expression of Clock and Bmal1 (P<0.05). The abdominal circumference and Lee's index of the medium-dose LD group decreased (8.61%, 5.04%), with their serum TC, TG and LDL-C decreasing (36.59%, 29.73%, 34.04%), Hb Alc decreasing by 24.37%, Clock and Bmal1mRNA expression increasing (159.17%, 228.58%) and protein expression increasing (52.09%, 151.33%). In conclusion, LD alleviated glucose and lipid metabolism disorders caused by a high-fat diet, which might be achieved through the upregulation of the liver Clock and Bmal1 gene expression. The results of this study provide a theoretical basis for using LD in the prevention and treatment of metabolic diseases and the development and utilization of functional health foods.

甘肃省中药原料质量监测技术服务中心建设基金资助项目（gszyzx201904）；西北营养与环境相关疾病中医药防控协同创新中心开放基金项目（ZYXT-20-01）