糖尿病并发抑郁症大鼠海马神经元凋亡情况及潜在机制研究

赵洪庆++杜青++凌佳++杨琴++徐雅岚++王宇红

摘要：目的 研究糖尿病并发抑郁症（DD）大鼠海马神经元凋亡情况，探讨其可能的分子机制。方法 采用高脂灌胃联合尾静脉注射链脲佐菌素建立糖尿病模型，随机分为糖尿病模型组和DD模型组，另取正常大鼠随机分为空白对照组和抑郁症模型组，抑郁症模型组和DD模型组继续给予28 d慢性不可预见性应激。造模结束后，采用Open-field实验和Morris水迷宫实验评价大鼠行为活动能力，HE染色观察大鼠海马病理改变，Western blot检测大鼠海马p-JNK、Bax、Bcl-2、Caspase8、Caspase3蛋白表达。结果 Open-field实验结果显示，各模型组大鼠自主活动能力显著下降，其中DD模型组大鼠较糖尿病模型组明显下降；Morris水迷宫实验结果显示，各模型组大鼠逃避潜伏期延长，其中DD模型组大鼠较糖尿病模型组明显延长；HE染色结果显示，DD模型组大鼠海马损伤最为严重；Western blot结果显示，各模型组大鼠较空白对照组p-JNK、Bax、Caspase8、Caspase3表达显著升高，Bcl-2表达显著降低，其中DD模型组差异更显著。结论 基于糖尿病，DD引起海马神经元凋亡，其机制可能与细胞凋亡相关蛋白p-JNK、Bax、Bcl-2、Caspase8、Caspase3等异常表达相关。

关键词：糖尿病；抑郁症；糖尿病并发抑郁症；神经元凋亡

DOI：10.3969/j.issn.1005-5304.2016.12.014

中图分类号：R228 文献标识码：A 文章编号：1005-5304（2016）12-0055-04

Study on Hippocampal Neuronal Apoptosis and Its Potential Mechanisms in Diabetic Rats with Depression ZHAO Hong-qing， DU Qing， LING Jia， YANG Qin， XU Ya-lan， WANG Yu-hong （Hunan University of Chinese Medicine， Training Bases， Hunan Key Laboratory of Chinese Materia Medica Powder and Innovative Drugs Established by Provincial and Ministry， Changsha 410208， China）

Abstract： Objective To study hippocampal neuronal apoptosis in rats with diabetes mellitus and depression （DD）； To explore its potential molecular mechanisms. Methods High-fat fed combined with intravenous injection of STZ was used to establish the models of diabetic rats， and then the models were divided into diabetes group and DD group after modeling successfully. Normal rats were randomly divided into control group and depression group. Chronic unforeseeable stress was continuously given to depression group and DD group. Open-field test and Morris water maze were used to evaluate the behavior activity of rats in each group； HE staining was used to detect pathological changes in hippocampus of rats； Western blot was used to disclose the protein expression of p-JNK， Bax， Bcl-2， Caspase8， and Caspase3. Results Open-field test results showed that the independent activity of rats decreased significantly in each model group， which decreased significantly in the DD group； Morris water maze results showed longer escape latency in model rats， which increased obviously in DD group； HE staining results suggested that the damage of hippocampus was the most severe in DD rats. Western blot results showed that compared with normal group， the expressions of apoptosis protein of p-JNK， Bax， Caspase8， and Caspase3 in each model group increased significantly and Bcl-2 expression decreased significantly， among which the difference in the DD group was the most obvious. Conclusion Hippocampal neuronal apoptosis caused by DD is based on diabetes， which mechanism may be related to abnormal expressions of p-JNK， Bax， Bcl-2， Caspase8， and Caspase3.

Key words： diabetes mellitus； depression； diabetes mellitus with depression； neuronal apoptosis

基金项目：国家自然科学基金（81373578、81403379、81573965）

通讯作者：王宇红，E-mail：wyh107@126.com

糖尿病并发抑郁症（diabetes mellitus with depression，DD）继发于糖尿病，具有危害大、自杀率高的特点。海马是与学习记忆密切相关的大脑组织，同时也是大脑中一个容易受到攻击的部位，其是脑内受糖尿病影响的首个组织，而且是抑郁症发生的首要部位。……