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[摘要]
目的 研究厚朴酚对抑郁模型大鼠海马神经可塑性的影响及其相关机制。方法 SD大鼠采用慢性温和不可知应激(CUMS)制备抑郁模型,ig给予不同剂量的厚朴酚(20、40 mg/kg),阳性对照组给予氟西汀(20 mg/kg),共给药28 d。观察各组大鼠自发活动、强迫游泳时间、糖水偏好程度3项行为学指标;荧光定量PCR检测各组大鼠脑内海马、皮质、纹状体区域的微管相关蛋白-2(MAP-2)、神经生长相关蛋白-43(GAP43)、突触素(SYP)的mRNA表达;免疫组化法检测大鼠海马区域MAP-2、GAP43、SYP蛋白表达水平;免疫印迹法检测各组大鼠脑内海马区域MAP-2、p-MAP-2及磷酸化细胞外信号调节激酶(p-ERK)蛋白表达水平。结果 模型组大鼠自发活动减少、糖水偏好降低、强迫游泳不动时间延长,造模成功。与模型组比较,厚朴酚各剂量可以显著提高大鼠自发活动能力,增加慢性应激大鼠糖水消耗量,减少慢性应激大鼠在强迫游泳中的不动时间(P<0.05、0.01);提高慢性应激所致的大鼠海马区MAP-2 mRNA及蛋白水平的降低(P<0.05);促进大鼠脑内海马区p-MAP-2蛋白表达(P<0.05),显著提高p-ERK的表达(P<0.05)。结论 厚朴酚可以通过ERK通路影响MAP-2的磷酸化,增加MAP-2的表达,从而影响神经元的可塑性,发挥其抗抑郁作用。
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[Abstract]
Objective To investigate the effect and mechanism of magnolol on hippocampal neuroplasticity in depression model rats. Methods In this study, depression model rats were prepared with unpredictable chronic mild stress (UCMS), and was given different doses of magnolol (20, 40 mg/kg) for 28 d. The rats in the positive control group were given fluoxetine (20 mg/kg) for 28 d. The ameliorative effects of magnolol on symptom of depression were investigated through behavior tests including open-field test, sucrose preference test, and forced-swimming test. The mRNA levels of Map-2, Gap43, and SYP in the hippocampus, cortex and striatum of rats in each group were detected by qRT-PCR, and the localization and expression of MAP-2, GAP43, and SYP in the hippocampus were observed by immunohistochemical staining analysis. The quantitative analysis of MAP-2, p-MAP-2, and p-ERK in hippocampus of rats in each group were further analyzed by Western blotting. Results UCMS was able to decrease the sucrose preference index, reduce locomotor activity and increase the immobility time in the forced swimming test. Compared with model group, magnolol significantly increased the spontaneous activity of rats, increased the consumption of sugar and water, and decreased the immobility time of chronic stress rats in forced swimming (P < 0.05, 0.01). Magnolol reversed MAP-2 mRNA and protein level in the hippocampus, increased phosphorylated MAP-2 expression in the hippocampus (P < 0.05), and significantly restored the p-ERK expression (P < 0.05). Conclusion Magnolol can affect the phosphorylation of MAP-2 through ERK pathway and increase the expression of MAP-2, thus affecting the neuronal plasticity and exerting its antidepressant effect.
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