目的: 脑血管修复在脑卒中后神经功能恢复过程中发挥关键作用, 然而促进其修复的有效策略及潜在机制尚不明确.本研究旨在探讨脑卒中后电针(EA)干预是否能够促进脑血管修复并改善神经功能, 并进一步阐明其可能的作用机制. 方法: 8周龄雄性C57BL/6J小鼠通过光化学法制备脑缺血模型, 造模后随机分为模型组,连续波电针组EA(Co)及疏密波电针组EA(SD), 每组10只;另设假手术对照组(Control), 含小鼠10只.电针组小鼠接受为期4周的电针干预, 每周5次, 每次20 min;刺激穴位为双侧“内关(PC6)”与“三阴交(SP6)”, 其中患侧连接电针仪进行刺激.电刺激参数为电流1 mA, 疏密波频率2/10 Hz,连续波频率2 Hz或50 Hz.光化学栓塞模型制备24 h后, 通过激光散斑对比成像与TTC染色验证缺血模型的建立和脑损伤程度.电针干预4周后, 采用黏附去除实验,悬挂实验及高架十字迷宫实验评估各组实验小鼠的神经功能相关行为学表现;免疫荧光染色技术检测脑梗死周围区域神经元活性,脑微血管重塑,内皮细胞增殖,血管基底膜和内皮糖萼相关修复指标的变化. 结果: 与健侧脑区相比, 模型小鼠梗死侧脑区血流灌注更低( P 0.05).(2)悬挂实验中, 模型组小鼠肌力表现显著低于假手术组( P 0.05).(4)小鼠脑梗死灶周围区神经元存活分析显示, 与假手术组相比, 模型组Nissl⁺/NeuN⁺ 共标的神经元密度较低( P 0.05).(5)脑血管结构分析显示, 模型组梗死灶周围区脑血管体积,分支密度及长度均低于假手术组(均 P 0.05);电针干预后, 该指标升高(均 P 0.05).(7)脑血管内皮糖萼(Lectin标记)及基底膜Ⅳ型胶原蛋白(Collagen IV)表达水平均较假手术组低(均 P 0.05). 结论: 电针可通过调节脑微血管重构,内皮细胞增殖,血管基底膜及内皮糖萼完整性, 促进缺血性脑卒中后的脑血管修复及神经功能恢复.其中, 连续波电针在脑血管修复程度方面优于疏密波电针.本研究为电针作为卒中后康复的潜在疗法提供了机制依据, 并提示刺激波形优化可提升其疗效, 具有一定临床转化潜力. 关键词: 缺血性脑卒中;电针;脑血管;神经功能障碍 : Cerebrovascular repair plays a crucial role in promoting post-stroke neurological recovery. However, effective strategies to enhance cerebrovascular repair and the underlying mechanisms remain elusive. Here, we investigated whether post-stroke electroacupuncture (EA) treatment could promote cerebrovascular repair and thereby improve neurological function, as well as the potential mechanisms involved. : Eight-week-old male C57BL/6J mice were subjected to photothrombosis-induced brain ischemia. Following successful model induction, the mice were randomly assigned to the model group, the EA continuous wave group (EACo), and the EA dense-sparse wave group (EASD), with 10 animals in each group. A sham-operated group (n = 10) served as the control. The EA groups received a 4-week EA intervention targeting the acupoints "Neiguan(PC6)" and "Sanyinjiao(SP6)". EA was administered five times per week with bilateral stimulation, and the affected side was connected to the EA device. The EA(SD) group received stimulation at 2/10 Hz, whereas the EA(Co) group received continuous wave stimulation at 2 Hz or 50 Hz; both were delivered at an intensity of 1 mA for 20 min per session. Twenty-four hours after photothrombosis induction, laser speckle contrast imaging and 2,3,5-triphenyltetrazolium chloride staining were performed to confirm model establishment and cerebral ischemic injury. Neurological function was evaluated using behavioral tests, including the adhesive removal test, hanging wire test, and elevated plus maze test. Immunofluorescence staining was performed to assess neuronal viability, cerebral microvascular structure, endothelial cell proliferation, and vascular repair markers in the peri-infarct cortex. : Significant reductions in cerebral blood perfusion ( P 0.05). (2) In the wire hanging test, the model group exhibited significantly lower muscle strength scores than the sham group ( P 0.05). (4) Immunofluorescence staining showed a significantly reduced density of Nissl⁺/NeuN⁺ double-labeled neurons in the peri-infarct regions of the model group compared with the control group ( P 0.05). (5) In terms of cerebrovascular structure, the model group exhibited significantly reduced vascular volume, microvascular branching density, and microvascular length in the peri-infarct regions compared with the control group (all P 0.05). Following EA treatment, this density was significantly increased compared with the model group ( P 0.05). (7) Compared with the control group, the model group exhibited significant reductions in lectin-labeled glycocalyx in vessels and basement membrane protein collagen IV expression (all P 0.05). : This study demonstrates that EA promotes cerebrovascular repair and neurological recovery after ischemic stroke by enhancing microvascular remodeling, stimulating endothelial proliferation, and restoring basement membrane and glycocalyx integrity. EA(Co) is more effective than EA(SD) in repairing vascular structure. These findings provide mechanistic evidence that EA is a promising therapeutic approach for post-stroke rehabilitation and suggest that waveform optimization may enhance its clinical efficacy.
Lin et al. (Sun,) studied this question.