开心散和当归芍药散对高脂饲料喂养的慢性应激大鼠糖脂代谢的影响及HPA轴相关机制

Effects and HPA Axis Related Mechanism of Kaixin-San and Danggui-Shaoyao-San on Glucose and Lipid Metabolism in Chronic Stress Rats with High-fat Diet

目的:探讨开心散和当归芍药散对高脂饲料喂养的慢性应激大鼠糖脂代谢的影响及潜在机制。方法:50只Wistar雄性大鼠随机分为正常对照组、高脂加应激模型组、褪黑素组(20 mg/kg)、开心散组(445 mg/kg)和当归芍药散组(3 360 mg/kg),灌胃给药。除正常对照组外,各组大鼠给予高脂饲料喂养,并于每日给药1 h后进行应激处理,连续6 w。每日记录大鼠体质量,给药3 w后收集24 h尿液,测定皮质酮水平。给药6 w后进行大鼠腹腔糖耐量(IVGTT)试验,后处死大鼠,测定血清空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素(INS)、促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)、褪黑素(MLT)水平,并测定大鼠肾上腺质量、肝糖原和肌糖原水平,计算肾上腺指数、胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI)。结果:与正常对照组比较,模型组大鼠体质量、IVGTT(120min)及血清CORT水平显著降低,血清TG、TC、LDL-C及尿液CORT水平显著升高。开心散和当归芍药散对上述指标具有调节作用。结论:开心散和当归芍药散可能通过促进MLT分泌和调节HPA轴活性改善模型大鼠的糖脂代谢紊乱。

Objective： To study the effects and potential mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats fed with high-fat diet. Methods： 50 male Wistar rats were randomly divided into normal control group（ distilled water）,high-fat diet with chronic stress group（ distilled water）,melatonin group（ 20 mg/kg）,Kaixin-San group（ 445 mg/kg）and Danggui-Shaoyao-San group（ 3 360 mg/kg）. All drugs were orally administered. In addition to the normal control group,each group of rats were fed with high-fat diet. Simultaneously,stress were carried out after drugs administration 1 h daily. The duration was lasted for six weeks. The rat body weight daily was recorded,and the 24 h period urine was collected to detect the level of urine corticosterone（ CORT） after three weeks. The level of plasma intraperitoneal glucose tolerance（ IVGTT） was detected after six weeks. Finally,rats were executed,and serum fasting blood glucose（ FBG）,triglyceride（ TG）,total cholesterol（ TC）,low-density lipoprotein cholesterol（ LDLC）,high density lipoprotein cholesterol（ HDL-C）,insulin（ INS）,adrenocorticotropic hormone releasing hormone（ CRH）,adrenocorticotropic hormone（ ACTH）,CORT and melatonin（ MLT） were determined. The weight of adrenal gland,liver glycogen and muscle glycogen levels were detected. The adrenal gland index,Homeostasis Model Assessment of Insulin Resistance（ HOMA-IR） and insulin sensitivity index（ ISI） were calculated. Results： Compared with normal group,model rats body weight,IVGTT（ 120 min）,plasm CORT were decreased significantly. Serum TG,TC,LDL-C and urine CORT after three weeks were increased significantly. Kaixin-San and DangguiShaoyao-San could regulate the above indexes. Conclusion： Kaixin-San and Danggui-Shaoyao-San may regulate the activity of HPA axis,and improve glucose and lipid metabolism disorder in model rats by increasing melatonin secretion.