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目的 通过构建雄性去势小鼠动物模型，初步观察雄激素替代治疗(TRT)对去势小鼠行为学、血清和组织病理的影响，并探讨雄激素对认知功能的作用。方法 40只6月龄雄性C57/BL6J小鼠随机分为假手术组、去势组、丙酸睾酮(0.5、1.0 mg/kg)治疗组，每组10只。经去势及予以不同浓度的丙酸睾酮(0.5、1.0 mg/kg)皮下注射进行TRT后，通过Morris水迷宫(MWM)实验、避暗实验检测各组小鼠学习记忆能力，ELISA检测小鼠血清睾酮与血清脑源性神经营养因子(BDNF)的表达，通过HE染色观察小鼠海马组织病理学变化。结果 常规项目观察：各组动物各时间点体质量差异无统计学意义。MWM实验：与去势组相比，假手术组、丙酸睾酮(0.5、1.0 mg/kg)治疗组第4、5天的逃避潜伏期显著缩短(P<0.05)，平台穿梭次数、目标象限停留时间显著增加(P<0.05)。避暗实验：假手术组、丙酸睾酮(1.0 mg/kg)治疗组避暗错误次数显著降低(P<0.05)，假手术组、丙酸睾酮(0.5、1.0 mg/kg)治疗组避暗潜伏期均显著增加(P<0.05)。血睾酮及血BDNF检测：假手术组、丙酸睾酮(0.5、1.0 mg/kg)治疗组血清睾酮、血清BDNF浓度均显著上升(P<0.01)。HE染色：与假手术组相比，去势组小鼠海马各区神经元密度略有降低；丙酸睾酮(0.5 mg/kg)治疗组小鼠CA1和CA3区神经元排列较去势组凋亡细胞减少；丙酸睾酮(1.0 mg/kg)治疗组小鼠CA3区锥体细胞层排列较去势组紧密，凋亡细胞减少。结论 TRT可以改善去势雄性小鼠的学习记忆能力，可能是通过影响小鼠海马BDNF通路而实现的。
Abstract：Objective To establish a castrated male mouse model and to preliminarily investigate the effects of tes‑tosterone replacement therapy(TRT) on behavior, serum indices, and histopathological changes in castrated mice, as well as to explore the role of androgens in cognitive function.Methods Forty 6-month-old male C57/BL6J mice were randomly divided into sham operation group, castration group, testosterone propionate(0.5,1.0 mg/kg) treated group, with 10 mice in each group.Following castration and subcutaneous administration of testosterone propionate at different doses(0.5 and 1.0 mg/kg) for TRT, learning and memory abilities were as‑sessed using the Morris water maze(MWM) test and the passive avoidance test.Serum testosterone and serum brain-derived neurotrophic factor(BDNF) levels were measured by ELISA, and histopathological changes in the hippocampus were examined using hematoxylin-eosin(HE) staining.Results Routine observations: there were no statistically significant differences in body weight among groups at any time point.MWM test: compared with castration group, sham operation group and testosterone propionate-treated groups(0.5, 1.0 mg/kg) showed sig‑nificantly reduced escape latency on days 4 and 5(P<0.05), while the number of platform crossings and the time spent in the target quadrant significantly increased(P<0.05).Passive avoidance test: the number of passive avoid‑ance errors significantly decreased in sham operation group and testosterone propionate(1.0 mg/kg)-treated group(P<0.05), and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups(0.5, 1.0 mg/kg)(P<0.05).Serum testosterone and serum BDNF assays: serum tes‑tosterone levels and serum BDNF concentrations significantly increased in sham operation group and testosterone propionate-treated groups(0.5, 1.0 mg/kg)(P<0.01).HE staining: compared with sham operation group, neu‑ronal density in all hippocampal subregions was slightly reduced in castration group; in the testosterone propionate(0.5 mg/kg)-treated group, neuronal arrangement in the CA1 and CA3 regions was improved and apoptotic cells were reduced compared with castration group; in testosterone propionate(1.0 mg/kg)-treated group, the pyrami‑dal cell layer in the CA3 region was more compactly arranged, with fewer apoptotic cells than in castration group.Conclusion TRT improves learning and memory performance in castration male mice, potentially through modu‑lation of hippocampal BDNF signaling pathways.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.03.010
中图分类号:R338
引用信息:
[1]张雅琪,惠灿灿,任芳,等.雄激素对去势雄性小鼠认知功能的影响[J].安徽医科大学学报,2026,61(03):455-461.DOI:10.19405/j.cnki.issn1000-1492.2026.03.010.
基金信息:
安徽省高校自然科学研究重点项目（编号：2022AH051141）~~
2026-02-09
2026-02-09
2026-02-09