慢性应激对2型糖尿病大鼠HPA轴紊乱及海马损伤的影响

Effects of Chronic Stress on HPA Axis and Hippocampus Dysfunction Impaired in Type 2 Diabetic Rats

目的:探讨慢性应激对2型糖尿病大鼠HPA轴紊乱及海马损伤的影响。方法:采用高脂灌胃联合尾静脉注射链脲佐菌素(STZ)的方法制备2型糖尿病动物模型并随机分为两组:一组给予慢性应激3周,另一组不进行慢性应激;同时以空白对照组及慢性应激组为对照。造模结束后,Morris水迷宫测定动物空间学习记忆能力;ELISA法测定血浆皮质酮(CORT)、促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放激素(CRH)水平;HE染色观察海马、下丘脑、垂体和肾上腺形态学变化。结果:与正常组比较,糖尿病组、慢性应激组及糖尿病联合慢性应激组大鼠水迷宫实验逃避潜伏期(EL)延长,空间探索时间(SET)缩短;血浆CORT、ACTH、CRH水平升高;海马、下丘脑、垂体和肾上腺形态结构呈现不同程度的器质性改变;但是糖尿病联合慢性应激组大鼠各项指标变化程度具有显著性意义(P<0.05)。结论:慢性应激可导致糖尿病大鼠HPA轴紊乱及海马损伤,大鼠学习记忆能力受损可能与此有关。

Objective：To investigate the effects of chronic stress on HPA axis and hippocampus dysfunction in type 2diabetic rat. Method：Type 2 diabetic rat model was established by high -fat diet with tail vein injection of streptozotocin （STZ）. Model rats were randomly divided into 2 groups： one group received chronic stress for 3 weeks while the other group without it. Three weeks later, spatial learning and memory was measured in Morris water maze. The corticosterone （ CORT）, adrenocorticotrophic hormone （ ACTH）, corticotropin releasing hormone （CRH） of plasma were detected with ELISA. Hippocampus, hippocampus, pituitary and adrenal tissue were stained with hematoxylin- eosin （HE） and examined microscopically. Result：Compared with control group, the evasive latency （EL） was longer and space exploration time（SET） was shorter in Morris water maze. CORT, ACTH and CRH of plasma were higher; hippocampus, hypothala- mus,pituitary and adrenal tissue showed organic changes in diabetic group, chronic stress group and combination of dia- betic and chronic stress group. However, the results of above index in group that combination of diabetic and chronic stress were significant different from those of the control group （ P 〈 0. 05 ）. Conclusion ： Chronic stress could accelerate the dysfunction of HPA axis and hippocampus in diabetic rats, which may be related to the damage of spatial learning and memory.