Zhang Yun, Gao Shiqing, Lin Ling, Zheng Yongbing
The Technology of Fujian Normal University College of Education, Fuzhou, China.
Preventive Treatment Center of Outpatient Department, Fujian Academy of Traditional Chinese Medicine, Fuzhou, China.
Ann Med Surg (Lond). 2025 Jul 25;87(9):5512-5521. doi: 10.1097/MS9.0000000000003628. eCollection 2025 Sep.
Ischemic stroke (IS) is a common disease that can cause cognitive dysfunction. Electroacupuncture (EA) is an effective way to alleviate cognitive dysfunction, but its molecular regulatory mechanism is still unclear. Long noncoding RNA-MEG3 (MEG3) is an important factor in the incidence and progression of IS. Herein, we explored the mechanism of EA in IS.
A middle cerebral artery occlusion (MCAO) model was established in Sprague-Dawley rats to simulate IS , followed by electroacupuncture (EA) therapy. AAV-control and AAV-MEG3 were injected into the lateral ventricle of rats. All rats except for the sham group underwent MCAO. EA was performed at Shenting and Baihui points for 30 min, once a day for 14 days. The MEG3 and miR-4640-3p levels in brains were measured by qRT-PCR. Dual-luciferase reporter analysis validated the relationship between MEG3 and miR-4640-3p. The Morris water maze test and the neurological function test were carried out. The pathological morphology of the brain tissue was evaluated by H&E staining. Apoptotic cells in brains were examined utilizing TUNEL staining. The contents of Bax, Bcl-2, caspase-3, and CytC were assessed by western blot.
EA treatment reduced the content of MEG3 but enhanced miR-4640-3p levels in MCAO rats. MEG3 was a sponge for miR-4640-3p. EA treatment alleviated cognitive dysfunction in MCAO rats by inhibiting MEG3. EA treatment reduced MCAO-induced neural damage and apoptosis by inhibiting MEG3.
EA improved cognitive dysfunction in IS rats by adjusting the MEG3/miR-4640-3p axis, suggesting that EA may be an effective potential therapeutic strategy for improvement of cognitive dysfunction in IS. This study provided a more reliable experimental basis for clinical EA treatment of IS patients.
缺血性脑卒中（IS）是一种可导致认知功能障碍的常见疾病。电针（EA）是缓解认知功能障碍的有效方法，但其分子调控机制仍不清楚。长链非编码RNA-MEG3（MEG3）是IS发生和发展的一个重要因素。在此，我们探讨了电针治疗IS的机制。
在Sprague-Dawley大鼠中建立大脑中动脉闭塞（MCAO）模型以模拟IS，随后进行电针治疗。将腺相关病毒对照（AAV-control）和腺相关病毒-MEG3（AAV-MEG3）注入大鼠侧脑室。除假手术组外，所有大鼠均接受MCAO手术。于神庭穴和百会穴进行电针治疗30分钟，每天1次，共14天。采用qRT-PCR检测大脑中MEG3和miR-4640-3p水平。双荧光素酶报告基因分析验证MEG3与miR-4640-3p之间的关系。进行莫里斯水迷宫试验和神经功能测试。通过苏木精-伊红（H&E）染色评估脑组织的病理形态。利用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色检测大脑中的凋亡细胞。通过蛋白质免疫印迹法评估Bax、Bcl-2、半胱天冬酶-3（caspase-3）和细胞色素C（CytC）的含量。
电针治疗降低了MCAO大鼠中MEG3的含量，但提高了miR-4640-3p水平。MEG3是miR-4640-3p的海绵。电针治疗通过抑制MEG3减轻了MCAO大鼠的认知功能障碍。电针治疗通过抑制MEG3减轻了MCAO诱导的神经损伤和细胞凋亡。
电针通过调节MEG3/miR-4640-3p轴改善了IS大鼠的认知功能障碍，提示电针可能是改善IS患者认知功能障碍的一种有效的潜在治疗策略。本研究为临床电针治疗IS患者提供了更可靠的实验依据。
