基础医学与临床 ›› 2025, Vol. 45 ›› Issue (7): 889-896.doi: 10.16352/j.issn.1001-6325.2025.07.0889

• 研究论文 • 上一篇    下一篇

STAT3介导A2表型星形胶质细胞极化缓解1型糖尿病大鼠周围神经痛

范婷婷, 李慧莉, 郭瑞娟, 马丹旭, 王云*   

  1. 首都医科大学附属北京友谊医院 麻醉科,北京 100050
  • 收稿日期:2025-03-24 修回日期:2025-05-20 出版日期:2025-07-05 发布日期:2025-06-24
  • 通讯作者: *wangyun129@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金青年科学基金(82301410)

STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats

FAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun*   

  1. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
  • Received:2025-03-24 Revised:2025-05-20 Online:2025-07-05 Published:2025-06-24
  • Contact: *wangyun129@ccmu.edu.cn

摘要: 目的 探究上调信号转导和转录激活因子3(STAT3)介导A2表型反应性星形胶质细胞极化对1型糖尿病(T1DM)周围神经痛的影响。方法 在1型糖尿病神经痛大鼠脊髓行鞘内注射STAT3过表达慢病毒(每次30 μL,连续2 d)和等量空白对照病毒,最终分为对照组control、T1DM组、T1DM+vector组和T1DM+STAT3 OE组。通过测定机械痛、热痛观察痛性糖尿病神经痛(PDN)是否发生变化;流式细胞分选各组星形胶质细胞,RT-qPCR确定星形胶质细胞的表型;免疫荧光染色确定A2表型星形胶质细胞在脊髓背角的比例,观察各组脊髓背角内A2表型星形胶质细胞的变化。结果 与对照组相比,T1DM组机械痛阈值(P<0.001)和热痛阈值显著降低(P<0.05); T1DM+STAT3 OE组机械痛阈值相较于T1DM组显著升高(P<0.001)。组织学分析显示,T1DM组星形胶质细胞发生退行性病理改变,T1DM+STAT3 OE组的脊髓背角星形胶质细胞激活,且向A2表型极化。结论 1型糖尿病神经痛大鼠脊髓STAT3通路受损。恢复STAT3表达促进星形胶质细胞增殖活化且向A2表型极化,从而达到缓解糖尿病神经痛的作用。

关键词: 1型糖尿病(T1DM), 痛性糖尿病神经痛(PDN), 信号转导和转录激活因子3(STAT3), A2表型反应性星形胶质细胞

Abstract: Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy. Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN). The rats were divided into four groups: control group, T1DM group, T1DM + vector group, and T1DM + STAT3 OE group. Paw withdrawal threshold and paw withdrawal latency were measured. Flow cytometry and RT-qPCR were used to sort astrocytes and determine the phenotype of reactive astrocytes. Immune-fluorescence staining microscopy was performed to observe the changes of A2 phenotype astrocytes in the spinal dorsal horn of each group. Results Compared to the control group, the mechanical (P<0.001) and heat thresholds (P<0.05) were significantly reduced in the T1DM group. The mechanical threshold was significantly increased in the T1DM+STAT3 OE group as compared to that in the T1DM group(P<0.001). Histolgical analysis showed degenerative pathological changes of spinal dorsal horn astrocytes in the T1DM group. Astrocytes in the T1DM+STAT3 OE group were activated and polarized toward the A2 phenotype. Conclusions The STAT3 pathway in the spinal dorsal horn astrocytes of rats with type 1 diabetic neuropathy is impaired. Restoring STAT3 expression promotes activation of astrocyte proliferation, activation, and polarization toward the A2 phenotype, thereby alleviating diabetic neuropathic pain.

Key words: type 1 diabetic mellitus (T1DM), painful diabetic neuropathy (PDN), signal transducer and activator of transcription 3 (STAT3), A2 phenotype reactive astrocytes

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