开心散、当归芍药散和圣约翰草对高脂加慢性应激大鼠行为学的影响及调节机制

Mechanism and effects of Kaixin Powder, Danggui Shaoyao Powder and Hypericum perforatum L. on the behavior of high fat rats with chronic stress

目的:探讨开心散、当归芍药散及圣约翰草对高脂加慢性应激诱导的胰岛素抵抗伴抑郁症模型大鼠行为学的影响。方法:50只Wistar雄性大鼠随机分为正常组、模型组、开心散组(445mg/kg)、当归芍药散组(3 360mg/kg)、圣约翰草组(300mg/kg)。除正常组外,各组大鼠给予高脂饲料喂养,并于每日给药1h后进行应激处理,连续6周。隔周测定空腹血糖(FBG),给药3周后收集24h尿液,测定皮质酮水平。给药第25、28天进行情绪唤醒及旷场试验,给药6周后处死大鼠,测定血清FBG、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)、胰岛素(INS)水平,计算胰岛素抵抗指数(HOMA-IR);并用Western Blot技术检测大鼠海马组织糖皮质激素受体(GR)蛋白表达。结果:与正常组比较,模型组大鼠情绪唤醒水平、水平与垂直运动得分降低,中央格停留时间延长(P<0.05,P<0.01);血清CORT水平及尿液CORT水平升高(P<0.05,P<0.01),GR蛋白表达显著降低(P<0.01)。开心散、当归芍药散和圣约翰草对上述指标具有调节作用,以GR蛋白最为明显(P<0.01)。结论:开心散、当归芍药散和圣约翰草可通过调节HPA轴活性,而改善高脂加慢性应激模型大鼠胰岛素抵抗水平和抑郁行为。

Objective： To study the effects of Kaixin Powder, Danggui Shaoyao Powder and Hypericum perforatumL. on ethology of IR（insulin resistance） rat models with depression induced by chronic stress and high-fat diet. Methods： Fifty male Wistar rats were randomly divided into normal control group, high fat and stress group, Kaixin Powder group（445mg/kg）, Danggui Shaoyao Powder group（3 360mg/kg） and Hypericum perforatum L. group（300mg/kg）. Rats in each group（except the normal control group） were given high fat feed and stimulation 1 hour after administration of drug every day for six weeks. Fasting blood glucose（FBG） was measured every other week and 24 h urine was collected after 3 weeks to detect the level of corticosterone. Emotional arousal test and open field test were carried out on the 25 th day and the 28 th day. The rats were killed after 6 weeks of drug administration and FBG, corticotropin releasing hormone（CRH）, adrenocorticotropic hormone（ACTH）, corticosterone（CORT） and insulin（INS） in serum were measured, and insulin resistance index was tested with HOMA-IR. The expression of glucocorticoid receptors（GR） protein in hippocampus of rats was determined by Western Blot. Results： Compared with the normal control group, the level of emotional arousal and the score of horizontal and vertical movement dropped and the time of staying in center was extended（P〈0.05, P〈0.01）; the levels of FBG, INS, ACTH, CRH, CORT in serum and HOMAIR increased（P〈0.01）, and the expression of GR protein was significantly lowered in the model group（P〈0.01）. Kaixin Powder, Danggui Shaoyao Powder and Hypericum perforatum L. had regulating effects on the above indexes. Conclusion： Kaixin Powder, Danggui Shaoyao Powder and Hypericum perforatum L. can improve IR level and alleviate depression of high fat rats withchronic stress by regulating the activity of HPA axis.