| 王翔锋， 李紫嫣，罗颖，蒋思敏，裴益聪，刘威.电针通过调节TREM2-DAP12信号通路改善大鼠术后认知功能的机制研究[J].中国医药科学,2025,(5):4-8 基金项目:国家自然科学基金项目基础提升计划专项课题（JCZX202306） |
| 电针通过调节TREM2-DAP12信号通路改善大鼠术后认知功能的机制研究 |
| Research on the mechanism of electroacupuncture improving postoperative cognitive function in rats by regulating TREM2-DAP12 signal pathway |
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| DOI： |
| 中文关键词: 围手术期神经功能紊乱；大鼠；电针；TREM2-DAP12信号通路；小胶质细胞 |
| 英文关键词:Perioperative neurocognitive disorder; Rats; Electroacupuncture; TREM2-DAP12 signal pathway; Microglia |
| 作者 | 单位 | | 王翔锋， 李紫嫣，罗颖，蒋思敏，裴益聪，刘威 | 福建中医药大学附属人民医院麻醉科，福建福州 350004 |
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| 中文摘要: |
| [摘要]目的 探讨电针通过调节髓样细胞触发受体2（TREM2）-衔接蛋白DAP12（DAP12）信号通路改善老年大鼠胫骨骨折术后认知功能的机制。方法 采用随机数表法将18月龄健康雄性SPF级大鼠20只分为电针组和对照组，每组各10只。电针组行百会、神庭穴电针刺激，对照组未行电针刺激。采用旷场实验评价大鼠认知功能；采用苏木精-伊红染色法观察海马组织细胞形态；采用TUNEL染色法观察海马组织细胞凋亡情况；采用酶联免疫吸附测定（ELISA）法测定血浆β淀粉样蛋白（Aβ）1-40、白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α浓度；采用Western blot法检测海马组织神经元特异性烯醇化酶（NSE）、S-100β蛋白、TREM2、DAP12蛋白表达。结果 认知功能：与对照组比较，电针组大鼠的活动时间、总路程、伸展时间均明显延长，平均速度显著提高（P < 0.05）。海马组织细胞形态和凋亡情况：对照组CA3区神经细胞核固缩、胞质深染，可见小胶质细胞吞噬神经元；电针组CA3区仅部分细胞胞质深染。与对照组比较，电针组神经元细胞凋亡数量明显减少（P < 0.05）。血浆Aβ1-40、IL-1β、IL-6、TNF-α浓度：与对照组比较，电针组大鼠血浆中Aβ1-40、IL-1β、IL-6、TNF-α表达水平明显降低（P < 0.05)。海马组织NSE、S-100β、TREM2、DAP12的表达水平：与对照组比较，电针组NSE、S-100β蛋白表达水平明显下降（P < 0.05），TREM2、DAP12的表达水平明显升高（P < 0.05）。结论 电针刺激百会、神庭穴可减轻老年大鼠胫骨骨折手术后海马神经元损伤和凋亡，减少神经认知障碍，其可能与电针激活TREM2-DAP12通路，促进小胶质细胞由M1型向M2型转变，减轻小胶质细胞炎症反应有关。 |
| 英文摘要: |
| [Abstract] Objective To investigate the mechanism of electroacupuncture regulating the signal pathway of triggering receptor expressed on myeloid cells 2 (TREM2)- DNAX activating protein of 12 kDa (DAP12) to improve the postoperative cognitive function of tibial fracture in aged rats. Methods A total of 20 healthy male specific pathogen free (SPF) rats aged 18 months were divided into the electroacupuncture group (n=10) and the control group (n=10) according to the random number table method. The electroacupuncture group was stimulated by Baihui (GV20) and Shenting (GV24) electroacupuncture, while the control group was not stimulated by electroacupuncture. The cognitive function of rats was evaluated by open field test. Hematoxylin-eosin staining was used to observe the morphology of hippocampal cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to observe the apoptosis of hippocampus. The plasma concentrations of amyloid β-protein (Aβ) 1-40, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). The expression of neuron-specific enolase (NSE), S-100β protein, TREM2 and DAP12 protein in hippocampus were detected by Western blot. Results Cognitive function: Compared with the control group, the activity time,total distance and stretching time of rats in the electroacupuncture group were all significantly prolonged, and the average speed was significantly increased (P < 0.05). Morphology and apoptosis of hippocampal cells: In the control group, the nuclei of neurons in cornu ammonis area 3 (CA3) were condensed and the cytoplasm was deeply stained, and microglia phagocytosis neurons could be seen. In the electroacupuncture group, only some cells in CA3 area were deeply stained. Compared with the control group, the number of neuronal apoptosis in the electroacupuncture group decreased remarkably, with statistically significant difference (P < 0.05). Plasma concentrations of Aβ1-40, IL-1β, IL-6 and TNF-α: Compared with the control group, the expression levels of Aβ1-40, IL-1β, IL-6 and TNF-α of rats in the electroacupuncture group were remarkably decreased, with statistically significant differences (P < 0.05). Expression levels of NSE, S-100β, TREM2 and DAP12 in hippocampus: Compared with the control group, the expression levels of NSE and S-100β protein in the electroacupuncture group decreased remarkably, with statistically significant differences (P < 0.05), while the expression levels of TREM2 and DAP12 increased remarkably, with statistically significant differences (P < 0.05). Conclusion Electroacupuncture stimulation of Baihui (GV20) and Shenting (GV24) can alleviate the injury and apoptosis of hippocampal neurons after tibial fracture surgery in aged rats, and reduce neurocognitive impairment, which may be related to electroacupuncture activating TREM2-DAP12 pathway, promoting the transformation of microglia from M1 type to M2 type, and alleviating the inflammatory reaction of microglia. |
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