左归降糖解郁方对糖尿病并发抑郁症大鼠HPA轴及海马糖皮质激素受体表达的影响

Effect of Zuogui Jiangtang Jieyu Recipe on the Expression of Glucocorticoid Receptor in HPA Axis and Hippocampus of Diabetic rats with Depression

目的:探讨复方中药左归降糖解郁方对糖尿病并发抑郁症(diabetes mellitus with depression,DD)大鼠HPA轴及糖皮质激素受体的调控作用,阐明其对海马组织的可能保护机制。方法:采用尾静脉注射STZ联合慢性应激建立DD大鼠模型,并按随机数字表法分为模型组、左归降糖解郁方低、中、高剂量组和阳性药组,同时以正常大鼠为对照组。末次给药后,测定各组大鼠血糖值及抑郁行为,病理切片染色观察大鼠海马组织损伤情况,ELISA试剂盒检测大鼠血浆促肾上腺皮质激素释放激素(corticotropin releasing hormone,CRH)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticosterone,CORT)水平,蛋白免疫印迹法(Western-blotting)检测大鼠海马糖皮质激素受体(glucocorticoid receptor,GR)表达。结果:左归降糖解郁方能显著降低模型大鼠的血糖值和抑郁样行为,海马病理损伤情况得以缓解,且血浆ACTH、CORT水平下降,海马GR蛋白表达上升。结论:左归降糖解郁方能明显改善DD大鼠血糖值和抑郁行为,保护海马神经元,其作用可能与上调GR表达密切相关。

Objective： To explore the regulation of HPA axis and glucocorticoid receptor in the compound Chinese medicine Zuogui Jiangtang Jieyu Prescription in Diabetic mellitus with depression and to clarify its possible mechanism of protection in hippocampus. Methods： Intravenous injection of streptozotocin combined with chronic stress continuously to replicate the diabetic rats model with depression, and divided into the model group, low, middle, and high dose of prescription groups, positive drug group. NormM rats were used as control group simultaneously. After the last administration, rats in each group were carried out the detection of blood glucose level and forced swimming test, using HE staining detect hippocampal damage. Elisa kit was used to disclose plasma CRH, ACTH and CORT levels, and Western-blotting to detect the expression of hippocampal glucocorticoid receptor. Results： After giving Zuogui Jiangtang Jieyu Prescription interventions, blood glucose significantly decreased in model rats, and its depression-like behavior alleviated, hippocampal damage be mitigated, ACTH, CORT and GR. levels be reversed. Conclusion： Zuogui Jiangtang Jieyu Prescription could obviously improve the blood glucose and depression-like behaviors in diabetic rats with depression, and protected hippocampal neurons, which role might be associated with up-regulated expression of GR.