杨蕙 王宇红 杜青 韩远山 孟盼 刘检 刘林 赵洪庆

摘要：目的 研究左歸降糖解郁方对糖尿病并发抑郁症模型大鼠海马星形胶质细胞神经营养功能的保护作用。方法 采用复合方法建立糖尿病并发抑郁症大鼠模型。实验大鼠随机分为模型组、阳性药组和左归降糖解郁方高、中、低剂量组，每组12只，另取12只SD大鼠作为正常组。各给药组给予相应药物灌胃，连续4周。旷场实验检测大鼠抑郁行为，免疫组化检测大鼠海马星形胶质细胞标记物特异性蛋白胶质纤维酸性蛋白（GFAP）及神经元细胞标记物微管相关蛋白2（MAP2）的表达，Western blot和RT-PCR检测大鼠海马星形胶质细胞营养分泌物脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、神经生长因子（NGF）表达。结果 与正常组比较，模型组大鼠活动次数明显减少，海马GFAP表达明显增加，MAP2、BDNF、GDNF、NGF表达明显减少；左归降糖解郁方干预后，模型大鼠抑郁行为明显改善，大鼠海马BDNF、GDNF、NGF、MAP2表达增加，GFAP表达明显减少。结论 左归降糖解郁方可有效改善大鼠海马星形胶质细胞的分泌功能，其可能通过增强星形胶质细胞的营养作用保护神经元，从而发挥抗抑郁作用。

关键词：左归降糖解郁方；糖尿病并发抑郁症；星形胶质细胞；神经营养；大鼠

DOI：10.3969/j.issn.1005-5304.2017.09.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）09-0043-05

Effects of Zuogui Jiangtang Jieyu Prescription on Neurotrophic Effects of Astrocytes in Diabetes Mellitus Rats with Depression YANG Hui1， WANG Yu-hong2， DU Qing2， HAN Yuan-shan1， MENG Pan2， LIU Jian1， LIU Lin1， ZHAO Hong-qing1 （1. First Hospital of Hunan University of Chinese Medicine， Changsha 410007， China； 2. Training Bases， Hunan Key Laboratory of Chinese Materia Medica Powder and Innovative Drugs Established by Provincial and Ministry， Changsha 410007， China）

Abstract： Objective To investigate the effects of Zuogui Jiangtang Jieyu Prescription on neurotrophic effects of astrocytes in diabetes mellitus rats with depression. Methods The diabetes mellitus with depression rat models were established by composite method， and then were randomly divided into 5 groups： model group， positive group， Zuogui Jiangtang Jieyu Prescription high-， medium-， low-dose groups， with 12 rats in each group. 12 normal rats were set as control group. Each administration group was given relevenat medicine for gavage for continuous 4 weeks. Open-field test was used to evaluate the depression-like behavior. The expression of GFAP in astrocyte and MAP2 in neuron were tested by immunohistochemistry. The expression of protein and mRNA of BDNF， GDNF， and NGF were tested by Western blot and RT-PCR. Results Compared with the control group， the activities of rats in model group were significantly reduced. The expression of GFAP increased， while the expressions of MAP2， BDNF， GDNF and NGF decreased. Compared with the model group， the depression-like behavior of rats in model group were significantly improved. The expression of GFAP decreased， while the expressions of MAP2， BDNF， GDNF and NGF increased， and GFAP decrseaed significantly. Conclusion The secretion function of astrocyte can be improved by Zuogui Jiangtang Jieyu Prescription. Its anti-depression and neuron-protection function might be correlated with the enhancement of neurotrophic effects of astrocytes.

Key words： Zuogui Jiangtang Jieyu Prescription； diabetes mellitus with depression； astrocyte； neurotrophy； rats

基金项目：国家自然科学基金（81403379、81373578、81573965、81603604）；湖南省自然科学基金（2016JJ4064）

通讯作者：王宇红，E-mail：philomena_yh@sina.com

研究发现，糖尿病并发抑郁症占糖尿病患者比例高达38.35%，其中轻度抑郁症为26%，中度为9.6%，中重度为2.9%，重度为0.7%[1]。目前治疗用药较少、研发滞后，与高患病率形成了鲜明对比。……