School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Acupuncture and Moxibustion Department, Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, Jiangxi 330008, China.
Brain Res Bull. 2024 Dec;219:111128. doi: 10.1016/j.brainresbull.2024.111128. Epub 2024 Nov 13.
Electroacupuncture (EA) at Shuigou (GV26) and Baihui (GV20) has shown therapeutic benefits for stroke patients. Given that natural killer (NK) cell infiltration into the brain significantly contributes to the exacerbation of cerebral ischemic injury, this study investigated the impact of EA at Shuigou (GV26) and Baihui (GV20) on post-ischemic brain infiltration and activation of NK cells.
Neurological deficit score, rotarod test, adhesive removal test, and TTC staining were used to evaluate the beneficial effects of EA in middle cerebral artery occlusion (MCAO) mice. The inhibitory effect of EA on STAT3 activation was assessed using Western blot. Flow cytometry was used to explore the impact of EA on post-ischemic brain infiltration of NK cells, as well as the activating receptor NKG2D expression and interferon-γ (IFN-γ) production by these infiltrated NK cells.
EA significantly alleviated neurological functional deficits and reduced brain infarction in MCAO mice. Abundant NK cells infiltrated into the ischemic hemisphere, but this infiltration was significantly suppressed by EA. Furthermore, EA attenuated NKG2D levels and reduced production of IFN-γ by NK cells in the ischemic brain. Notably, EA's inhibitory effect on post-ischemic NK cell brain infiltration and activation was comparable to that of STAT3 inhibition. The combination of EA and STAT3 inhibition did not result in further enhancement of the inhibitory effect. Moreover, the protective effects of EA against MCAO injury were abolished when STAT3 was activated.
Our findings suggest that EA at Shuigou (GV26) and Baihui (GV20) inhibits the post-ischemic brain infiltration and activation of NK cells through STAT3 inhibition, significantly contributing to its therapeutic effects against brain ischemia.
电针水沟（GV26）和百会（GV20）已显示出对中风患者的治疗益处。鉴于自然杀伤（NK）细胞浸润大脑显著加剧脑缺血损伤，本研究探讨了电针水沟（GV26）和百会（GV20）对缺血后大脑浸润和 NK 细胞激活的影响。
采用神经功能缺损评分、转棒试验、粘贴去除试验和 TTC 染色评估电针对大脑中动脉闭塞（MCAO）小鼠的有益作用。采用 Western blot 评估电针对 STAT3 激活的抑制作用。采用流式细胞术探讨电针对缺血后大脑 NK 细胞浸润以及这些浸润 NK 细胞表达激活受体 NKG2D 和产生干扰素-γ（IFN-γ）的影响。
电针显著减轻 MCAO 小鼠的神经功能缺损和脑梗死。大量 NK 细胞浸润缺血半球，但电针明显抑制了这种浸润。此外，电针减弱了缺血大脑中 NKG2D 水平，并减少了 NK 细胞 IFN-γ的产生。值得注意的是，电针对缺血后 NK 细胞脑浸润和激活的抑制作用与 STAT3 抑制相当。电针和 STAT3 抑制的联合使用并未导致抑制作用进一步增强。此外，激活 STAT3 时，电针对 MCAO 损伤的保护作用被消除。
我们的研究结果表明，电针水沟（GV26）和百会（GV20）通过抑制 STAT3 抑制缺血后大脑 NK 细胞浸润和激活，对脑缺血发挥治疗作用。
