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

Effects of Zuogui Jiangtang Jieyu Fang on Synaptic Function Plasticity in Hippocampal Neurons of Diabetes Mellitus with Depression Model Rats

目的针对NR受体亚型及其下游分子Ca MKII、Syn GAP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、Ca MKII、Syn GAP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Ca MKII、Syn GAP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、Ca MKII、Syn GAP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Ca MKII、Syn GAP的表达,保护海马神经元突触功能可塑性有关。

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 Ca MKII, Syn GAP. 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 NR2 A, NR2 B, Syn GAP and Ca MKII 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 NR2 A, NR2 B, Syn GAP and Ca MKII 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 NR2 A, NR2 B, Syn GAP and Ca MKII 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 Syn GAP and Ca MKII.