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引用本文:杜青,赵洪庆,王宇红,徐雅岚,杨蕙,孟盼.左归降糖解郁方对糖尿病并发抑郁症模型大鼠海马神经元突触功能可塑性相关蛋白的影响[J].中国现代应用药学,2016,33(5):521-525.
DU Qing,ZHAO Hongqing,WANG Yuhong,XU Yalan,YANG Hui,MENG Pan.Effects of Zuogui Jiangtang Jieyu Fang on Synaptic Function Plasticity in Hippocampal Neurons of Diabetes Mellitus with Depression Model Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(5):521-525.
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左归降糖解郁方对糖尿病并发抑郁症模型大鼠海马神经元突触功能可塑性相关蛋白的影响
杜青1, 赵洪庆1, 王宇红1,2, 徐雅岚1, 杨蕙2, 孟盼1
1.湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙 410007;2.湖南中医药大学第一附属医院,长沙 410007
摘要:
目的 针对NR受体亚型及其下游分子CaMKII、SynGAP的表达情况,探索左归降糖解郁方对糖尿病并发抑郁症模型大鼠海马神经元突触功能可塑性的影响。方法 复制糖尿病并发抑郁症大鼠模型并随机分为4组:模型组,阳性药组(二甲双胍0.18 g·kg-1+盐酸氟西汀1.8 mg·kg-1),左归降糖解郁方高、低剂量组(32.82,8.20 g·kg-1),以正常大鼠为空白对照组。采用Morris水迷宫检测大鼠的空间学习记忆能力,Western-blotting实验检测大鼠海马NR2A、NR2B、CaMKII、SynGAP的表达情况。结果 与空白对照组比较,模型组大鼠逃避潜伏期延长,空间探索时间减少(P<0.05),NR受体亚型NR2A、NR2B及CaMKII、SynGAP的表达明显减少(P<0.01);与模型组比较,阳性药组和左归降糖解郁方高剂量组逃避潜伏期显著缩短(P<0.05),空间探索时间显著增加(P<0.05),NR2A、NR2B、CaMKII、SynGAP的表达明显增多(P<0.05或0.01)。结论 左归降糖解郁方可以明显增强糖尿病并发抑郁症大鼠的学习记忆能力,改善认知功能障碍,缓解抑郁症状,该作用可能与调节海马NR受体亚型NR2A、NR2B及其下游分子CaMKII、SynGAP的表达,保护海马神经元突触功能可塑性有关。
关键词:  糖尿病并发抑郁症  左归降糖解郁方  NR2A  NR2B  CaMKII  SynGAP
DOI:
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基金项目:国家自然科学基金(81373578,81573965,81403379)
Effects of Zuogui Jiangtang Jieyu Fang on Synaptic Function Plasticity in Hippocampal Neurons of Diabetes Mellitus with Depression Model Rats
DU Qing1, ZHAO Hongqing1, WANG Yuhong1,2, XU Yalan1, YANG Hui2, MENG Pan1
1.Training Bases, Hunan Key Laboratory of Chinese Materia Medica Powder and Innovative Drugs Established by Provincial and Ministry, Changsha, 410007, China;2.The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China
Abstract:
OBJECTIVE To explore the effects of Zuogui Jiangtang Jieyu Fang on diabetes mellitus plasticity of synaptic function in hippocampal neurons of diabetes mellitus model rats with depression according to the expression of NR receptor subtype and its downstream molecular CaMKII, SynGAP. METHODS The diabetes mellitus with depression rat model was established, and the rats were randomly divided into 4 groups: model group, positive drug group (metformin 0.18 g·kg-1+fluoxetine hydrochloride 1.8 mg·kg-1), Zuogui Jiangtang Jieyu Fang high and low dose group (32.82, 8.20 g·kg-1), normal rats were in blank control group. Morris test was used to detect the behavior of the rats. The expression of NR2A, NR2B, SynGAP and CaMKII was detected by Western-blotting. RESULTS Compared with blank control group, the escape latencies were longer, the space exploration times were significantly shortened(P<0.05), and the expression of NR2A, NR2B, SynGAP and CaMKII were significantly increased(P<0.01) in model group. Compared with the model group, the escape latencies were significantly longer(P<0.05), the space exploration times were significantly shortened(P<0.05) and the expression of NR2A, NR2B, SynGAP and CaMKII were significantly decreased(P<0.05 or 0.01) in Zuogui Jiangtang Jieyu Fang group. CONCLUSION Zuogui Jiangtang Jieyu Fang can significantly enhance the learning and memory ability, improving cognitive dysfunction, and relieve the depressive symptoms in diabetes mellitus with depression model rats. The effect may be related with the protection of synaptic function in hippocampal neurons through regulating the expression of NR receptor subtype and its downstream molecules SynGAP and CaMKII.
Key words:  diabetes mellitus with depression  Zuogui Jiangtang Jieyu Fang  NR2A  NR2B  CaMKII  SynGAP
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