王钟毓,易仕军,彭烨鹏,等.心肌梗死对小鼠海马A1型星形胶质细胞介导的神经元坏死性凋亡及认知功能的影响[J].中华物理医学与康复杂志,2026,48(2):103-111
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| 心肌梗死对小鼠海马A1型星形胶质细胞介导的神经元坏死性凋亡及认知功能的影响 |
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| DOI：10.3760/cma.j.cn421666-20251207-01085 |
| 中文关键词: 心肌梗死 星形胶质细胞 坏死性凋亡 认知功能障碍 |
| 英文关键词: Myocardial infarction Astrocytes Necroptosis Cognitive impairment |
| 基金项目: |
| 作者 | 单位 | | 王钟毓 | 广西医科大学基础医学院病理生理学教研室,南宁 530021
湖北医药学院基础医学院生理学教研室,十堰 442000 | | 易仕军 | 湖北医药学院基础医学院生理学教研室,十堰 442000 | | 彭烨鹏 | 湖北医药学院基础医学院生理学教研室,十堰 442000 | | 倪双 | 湖北医药学院基础医学院生理学教研室,十堰 442000 | | 孙嘉楠 | 湖北医药学院基础医学院生理学教研室,十堰 442000 | | 刘湘 | 湖北医药学院基础医学院生理学教研室,十堰 442000 | | 陈龙 | 湖北医药学院附属国药东风医院中心试验室,十堰 442000 | | 唐俊明 | 湖北医药学院基础医学院生理学教研室,十堰 442000
湖北医药学院胚胎干细胞研究湖北省重点实验室,十堰 442000 | | 潘尚领 | 广西医科大学基础医学院病理生理学教研室,南宁 530021 |
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| 中文摘要: |
| 目的 探讨心肌梗死 (MI) 对小鼠海马 A1 型星形胶质细胞介导的神经元坏死性凋亡及认知功能的影响。方法 选取 6~8 周龄成年雄性 C57BL/6J 小鼠 25 只，按照随机数字表法分为假手术组 (Sham 组) 和心肌梗死组 (MI 组)，Sham 组 10 只，MI 组 15 只。MI 组采用左冠状动脉结扎法构建 MI 模型，Sham 组实施相同手术暴露但不结扎血管。术后 MI 组死亡 4 只、造模失败 1 只，最终两组均纳入 10 只。造模后 28d，进行心功能检测、认知功能评估（Morris 水迷宫、Y 迷宫及新事物识别实验），检测海马组织炎症因子水平，观察星形胶质细胞活化及神经元增殖与凋亡情况，检测 p-P38、P38 及 NLRP3 表达水平。结果 与 Sham 组比较，MI 组小鼠心功能显著下降，认知行为学测试显示逃避潜伏期延长、目标象限停留时间及穿越平台次数减少、迷宫自由交替率及新物体识别指数均下降（P<0.05）；海马组织 IL-1β 和 TNF-α 水平升高，A1 型星形胶质细胞活化增加，神经元数量减少，p-P38 及 NLRP3 表达上调。结论 MI 可增强小鼠海马组织炎症反应并诱导 A1 型星形胶质细胞极化，进而促进神经元坏死性凋亡，导致认知功能障碍。 |
| 英文摘要: |
| Objective To determine to what extent activation of A1-type astrocytes in the hippocampus contributes to cognitive impairment after myocardial infarction (MI) by promoting necroptotic neuron death. Methods Twenty-five adult male C57BL/6J mice aged 6 to 8 weeks were randomly divided into a sham operation group (Sham group) and a myocardial infarction group (MI group) with 10 mice in each. MI was induced in the MI group using ligation of the left coronary artery, while the Sham group underwent the same surgical exposure but without ligation of the vessels. At 28 days after the modeling, cardiac function tests and echocardiography were performed for both groups. Cognitive functioning was evaluated using the Morris water maze, Y-maze and novel object recognition tests. Inflammatory cytokines in the hippocampus were measured using ELISA. Astrocyte activation and proliferation and apoptosis of neurons in the hippocampus region were observed by immunofluorescence staining and TUNEL staining. The expression levels of p-P38, P38 and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) in the hippocampal tissue were detected by western blotting. Results Compared with the Sham group, the MI mice, on average, exhibited significantly impaired cardiac function, prolonged escape latency, reduced time spent in the target quadrant, fewer platform crossings, decreased spontaneous alternation in the Y-maze, and a lower novel object recognition index. Their level of IL-1β and TNF-α in the hippocampus was significantly higher, with greater activation of A1-type astrocytes, accompanied by reduced neuron counts and enhanced expression of p-P38 and NLRP3. Conclusions MI induces a pronounced inflammatory response and promotes A1-type astrocyte polarization in the hippocampus, which drives necroptotic neuron death and contributes to cognitive impairment. |
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