高脂饲料加STZ联合诱导的大鼠糖尿病模型HPA轴功能变化与糖脂代谢的关系

目的研究高脂饲料加小剂量STZ联合诱导的糖尿病大鼠HPA轴功能变化与糖脂代谢的关系。方法采用长期高脂饲料加STZ(30mg·kg-1ip)联合诱导的糖尿病模型,将其分为4组,即正常对照组、模型组、地黄寡糖(ROS)组和二甲双胍组,ROS组灌胃地黄寡糖(200mg·kg-1.d-1),二甲双胍组灌胃盐酸二甲双胍(200mg·kg-1.d-1);每周测定1次大鼠血糖和体重,给药4wk后收集24h尿液并断头处死,测定血浆中血脂(TC、TG、HDL-C)、胰岛素、CRH、ACTH、皮质酮及下丘脑中CRH、垂体中ACTH、24h尿液中尿糖及皮质酮(CORT)含量。结果与正常对照组相比,模型组血糖、尿糖、TC、TG均明显升高,肝糖原、HDL-C含量下降,地黄寡糖能逆转这些改变。同时模型与正常对照组相比,胰岛素和下丘脑中CRH下降明显,血浆中ACTH、CORT及垂体中ACTH、24h尿液中CORT总量都有所升高,ROS对其有一定的改善作用。结论高脂饲料加STZ诱导的糖尿病模型糖脂代谢紊乱可能与HPA的活性升高有关,中药地黄寡糖的降血糖作用可能与改善HPA功能有一定关系。

The function changes of HPA axis in diabetic rat model induced by high lipid food plus STZ and relation with glucose and lipid metabolism

Aim To investigate HPA axis change relation with glucose and lipid metabolism.Methods Wistar rats were injected intraperitoneally with STZ (30 mg·kg~(-1)) after fed with high lipid food for two months, then rats with blood glucose of over 15 mmol·L~(-1) were used in the experiment. Animals were divided into four groups: normal group, diabetic model group, treatment group (ROS 200 mg·kg~(-1) ·d~(-1) ig), and metformin group (200 mg·kg~(-1)·d~(-1) ig).Rats were decapitated after they had been administered ig for four weeks and were 24 hour urine collected.Plasma CRH, ACTH, corticosterone, hypothalamic CRH, ACTH of pituitary gland, 24 hour urinary corticosterone and plasma insulin were determined by ELISA and radio immunity kit respectively.Results In diabetic rat model induced by high lipid food and STZ, plasma and urinary glucose level and plasma TC, TG levels were increased, plasma HDL-C and hepatic glycogen content were reduced, which was synchronized with changes of higher pituitary ACTH, plasma and total 24 hour urine corticosterone excretion.Conclusion The disorder of glucose and lipid metabolism of model induced by high lipid food and low dose STZ may be linked to the change of HPA axis.The improvement of ROS on glucose and lipid metabolism in diabetic rats may be linked to the decrease of HPA axis activity.