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目的:探究香砂六君子汤对慢性应激抑郁模型小鼠行为、海马神经元损伤及海马突触体内游离Ca2+浓度的影响。方法:60只昆明雄性小鼠平均分为正常组、模型组、香砂六君子汤活性部位高、中、低剂量组(800,600,400 mg.kg-1)。采用长期不可预见性慢性应激小鼠抑郁模型,测定各组小鼠体重变化,Open-field法和糖水消耗实验测定各组小鼠的行为变化;N issl染色法观察海马CA1,CA3区神经元形态及锥体细胞数目;以Fura-2负载及荧光分光光度计检测海马突触体内游离Ca2+浓度。结果:与正常组比较,模型组小鼠呈现明显的抑郁样症状。香砂六君子汤活性部位高、中、低剂量组小鼠在第14,21天体重增长明显高于模型组,其中高、中剂量能增加抑郁小鼠的爬格数(P<0.05),但与剂量无对应关系;高剂量能增加抑郁小鼠的站立次数(P<0.001);低、中、高剂量能明显增加抑郁小鼠的糖水消耗量(P<0.01,P<0.01,P<0.001),并呈现一定的量效关系。高,中剂量组小鼠海马CA3区空泡明显减少,且锥体细胞数量显著增多(P<0.001);高、中剂量能明显降低抑郁小鼠海马突触体内游离Ca2+浓度(P<0.01,P<0.001)。结论:香砂六君子汤活性部位能改善小鼠的抑郁样行为;保护抑郁模型小鼠海马神经元损伤,其可能与香砂六君子汤活性部位抑制海马神经细胞外Ca2+内流,阻止Ca2+超载相关。
OBJECTIVE: To investigate the effects of Xiangsha Liujunzi Decoction on behavior, hippocampal neuronal injury and free Ca2+ concentration in hippocampal synaptosomes of chronic stress-depressed model mice. METHODS: Sixty Kunming male mice were equally divided into normal group, model group, Xiangsha Liujunzi Decoction active site high, middle and low dose groups (800, 600, 400 mg.kg-1). Using a long-term, unpredictable, chronic stress mouse model of depression, body weight changes were measured in each group, Open-field method and glucose consumption test were used to determine the behavioral changes in each group; Nissl staining was used to observe the hippocampal CA1, CA3 neurons. The morphology and number of pyramidal cells were detected. The free Ca2+ concentration in hippocampal synapse was detected by Fura-2 loading and fluorescence spectrophotometer. RESULTS: Compared with the normal group, the mice in the model group presented significant depression-like symptoms. The body weight of the mice in the high, middle and low dose groups of Xiangsha Liujunzi Decoction was significantly higher than that of the model group on the 14th and 21st days, and the high and medium doses could increase the number of crawling frames of depressive mice (P<0.05). However, there was no corresponding relationship with the dose; high doses increased the number of standing times in depressed mice (P<0.001); low, medium, and high doses significantly increased sugar consumption in depressed mice (P<0.01, P<0.01, P< 0.001), and show a certain dose-effect relationship. The vacuolization of the CA3 area in the hippocampus of mice in the high-and medium-dose groups was significantly reduced, and the number of pyramidal cells was significantly increased (P<0.001); high and medium doses could significantly reduce the concentration of free Ca2+ in hippocampal synaptosomes of depressed mice (P<0.01, P<0.001). Conclusion: The active fraction of Xiangsha Liujunzi Decoction can improve the depression-like behavior of mice and protect the hippocampal neurons from the depressive model mice. It may be related to the active fraction of Xiangsha Liujunzi Decoction inhibiting the extracellular Ca2+ influx of hippocampal neurons and preventing the Ca2+ overload. Related.