本研究旨在探讨磷酸二酯酶抑制剂咯利普兰对脑组织再生的影响。三甲基锡注射小鼠是通过单次注射三甲基氯化锡（2.2 mg/kg，腹腔注射）建立的海马组织再生动物模型。从注射三甲基锡后的第二天到采样前一天，每天进行咯利普兰给药（10 mg/kg，腹腔注射）。在实验 1 中，在强迫游泳测试后注射三甲基锡后第 7 天收集脑样本。在实验2中，在第3-5天施用溴脱氧尿苷（150mg/kg，腹膜内/天），并在注射三甲基锡后第21天取样。通常将样品包埋在石蜡中并获得切片用于组织病理学研究。在实验1中，咯利普兰治疗的小鼠在强迫游泳测试中表现出缩短的不动时间。组织病理学显示，咯利普兰治疗改善了齿状回神经元核阳性神经元的补充，同时磷酸化环AMP反应元件结合蛋白阳性细胞的百分比增加。此外，咯利普兰还降低了具有激活形态的离子钙结合衔接蛋白1阳性小胶质细胞的百分比以及肿瘤坏死因子-α表达细胞的数量。在实验2中，溴脱氧尿苷/神经元核的双重免疫荧光显示，咯利普兰治疗的小鼠中双阳性细胞有所增加。这些结果表明，咯利普兰通过增强新生神经元的存活和抑制神经炎症，有效促进脑组织再生。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。

This study aimed to investigate the effects of rolipram, a phosphodiesterase inhibitor, on brain tissue regeneration. Trimethyltin-injected mice, an animal model of hippocampal tissue regeneration, was created by a single injection of trimethyltin chloride (2.2 mg/kg, intraperitoneally). Daily rolipram administration (10 mg/kg, intraperitoneally) was performed from the day after trimethyltin injection until the day before sampling. In Experiment 1, brain samples were collected on day 7 postinjection of trimethyltin following the forced swim test. In Experiment 2, bromodeoxyuridine (150 mg/kg, intraperitoneally/day) was administered on days 3-5 and sampling was on day 21 postinjection of trimethyltin. Samples were routinely embedded in paraffin and sections were obtained for histopathological investigation. In Experiment 1, rolipram-treated mice showed shortened immobility times in the forced swim test. Histopathology revealed that rolipram treatment had improved the replenishment of neuronal nuclei-positive neurons in the dentate gyrus, which was accompanied by an increase in the percentage of phosphorylated cyclic AMP response element-binding protein-positive cells. In addition, rolipram had decreased the percentage of ionized calcium-binding adapter protein 1-positive microglia with activated morphology and the number of tumor necrosis factor-alpha-expressing cells. In Experiment 2, double immunofluorescence for bromodeoxyuridine/neuronal nuclei revealed an increase of double-positive cells in rolipram-treated mice. These results demonstrate that rolipram effectively promotes brain tissue regeneration by enhancing the survival of newborn neurons and inhibiting neuroinflammation.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.