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刘丹,蔺晓源,文诗仪,刘彤彤,孟盼.磷酸二酯酶4抑制剂咯利普兰对慢性应激抑郁模型大鼠学习记忆及海马突触可塑性的影响[J].湖南中医药大学学报英文版,2021,41(3):359-363.[Click to copy
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| 磷酸二酯酶4抑制剂咯利普兰对慢性应激抑郁模型大鼠学习记忆及海马突触可塑性的影响 |
| 刘丹,蔺晓源,文诗仪,刘彤彤,孟盼 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学医学院, 湖南 长沙 410208;湖南中医药大学科技创新中心, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨磷酸二酯酶4（phosphodiesterase 4，PDE4）抑制剂咯利普兰对慢性应激抑郁模型大鼠行为活动、学习记忆及海马突触可塑性的影响。方法 采用慢性温和不可预见性应激的方式建立抑郁模型，将SD大鼠随机分为4组，即空白组、抑郁模型组、氟西汀组、咯利普兰组。造模的同时，氟西汀组灌胃氟西汀（5.4 mg/kg），咯利普兰在实验的第1、7、14、21天腹腔注射给药，均按1.25 mg/kg给药，模型组腹腔注射等量生理盐水，观察咯利普兰对抑郁模型大鼠旷场、水迷宫的影响，ELISA检测血浆和海马组织中cAMP水平的变化，免疫组化观察各组大鼠海马突触素（synaptophysin，SYN）的表达，Western blot检测PI3K、p-CREB、BDNF的表达情况。结果 与空白组比较，模型组大鼠活动量下降（P<0.01），目标象限的穿越次数下降（P<0.05）、潜伏时间增加（P<0.01），血浆、海马组织中cAMP含量下降（P<0.01），海马SYN、BDNF、PI3K、p-CREB的表达下调（P<0.05或P<0.01）；与模型组比较，咯利普兰能显著增加抑郁模型大鼠的活动量（P<0.01），增加穿越目标象限的次数（P<0.05），降低目标象限的潜伏时间（P<0.05），增加血浆、海马组织中cAMP的含量（P<0.05或P<0.01），并能显著促进模型大鼠海马SYN、BDNF、PI3K、p-CREB的表达（P<0.05或P<0.01）。结论 咯利普兰能显著改善抑郁模型大鼠的学习记忆能力并能促进海马突触可塑性，其机制可能与调节海马BDNF-PI3K信号通络的相互作用紧密相关。 |
| 关键词: 抑郁症 咯利普兰 磷酸二酯酶4 海马 突触可塑性 学习记忆 |
| DOI：10.3969/j.issn.1674-070X.2021.03.007 |
| Received:August 28, 2020 |
| 基金项目:湖南省自然科学基金优秀青年项目（2020JJ3027）；湖南省科技创新人才计划优秀博士后创新人才项目（2020RC2060）；长沙市杰出创新青年培养计划（kq2009018）。 |
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| Effects of Phosphodiesterase 4 Inhibitor Rolipram on Learning, Memory and Synaptic Plasticity of Hippocampus in Rats of Chronic Unpredicted Mild Stress Model |
| LIU Dan,LIN Xiaoyuan,WEN Shiyi,LIU Tongtong,MENG Pan |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Medical College of Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the molecular mechanism of phosphodiesterase 4 (PDE4) inhibitor rolipram on behavioral activity, memory and hippocampal synaptic plasticity in chronic unpredicted mild stress (CUMS) rats. Methods The depressed rats were established by CUMS. SD rats were randomly divided into 4 groups:blank control group, depression model group, fluoxetine group and rolipram group. At the same time of modeling, fluoxetine group was given fluoxetine (5.4 mg/kg) by gavage, and roliplam group was given intraperitoneally at 1.25 mg/kg on day 1, 7, 14 and 21 of the experiment. Model group was injected intraperitoneally with the same amount of normal saline. The effects of rolipram on open field test and water maze test of depression model rats were observed. The changes of cAMP level in plasma and hippocampus were detected by ELISA. Synaptophysin (SYN) in hippocampus of rats was observed by immunohistochemistry, and PI3K, p-CREB, BDNF were detected by Western blot. Results Compared with normal group, the activity of rats in model group decreased (P<0.01), the number of crossing target quadrant decreased (P<0.05), the latency time increased (P<0.01), the content of cAMP in plasma and hippocampus decreased (P<0.01), and the expressions of SYN, BDNF, PI3K and p-CREB in hippocampus were down-regulated (P<0.05 or P<0.01). Compared with model group, rolipram could significantly increase the scores of activities of the depressed model rats (P<0.01), significantly promote the times of crossing the target quadrant (P<0.05), reduce the latency time of the target quadrant (P<0.05) and increase the content of cAMP in plasma, hippocampal tissue (P<0.05 or P<0.01), and can significantly promote the model of rat hippocampal SYN, BDNF, PI3K, and P-CREB (P<0.05 or P<0.01). Conclusion Rolipram can significantly improve the learning and memory ability of CUMS rats and promote synaptic plasticity of hippocampus, which may be closely related to the interaction between BDNF-PI3K signal pathway of hippocampal. |
| Key words: depression rolipram phosphodiesterase 4 hippocampus synaptic plasticity learning and memory |
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