Zhang Jun-Yu, Yu Jing-Jing, Li Cheng-Long, Mao Wei, Zhang Li-da, Tong Ting-Ting, Wang Jun-Li, Wu Hai-Yang, Zhang Guo-Qing, Ji Hai-Sheng, Wang Hai-Tao, Han Wei, Wang Ying
The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.
Graduate School, Anhui University of Chinese Medicine, Hefei 230031.
Zhen Ci Yan Jiu. 2025 Jul 25;50(7):773-781. doi: 10.13702/j.1000-0607.20240762.
To observe the effect of electroacupuncture (EA) on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)/NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway of the cerebral cortex in rats with cerebral ischemia reperfusion injury and investigate the underlying mechanisms of EA in improving cerebral ischemia reperfusion injury.
A total of 45 SD rats were randomly assigned into sham-operation group, model group and EA group, with 15 rats in each group. The modified thread embolism method was used to establish the model of cerebral ischemia reperfusion injury. Rats in the EA group received EA at "Baihui" (GV20), "Fengfu" (GV16), and "Dazhui" (GV14) for 20 min, once daily for 7 consecutive days. The modified neurological severity score (mNSS) was used to assess the neurological deficit condition. TTC staining was used to detect the percentage of cerebral infarction. HE staining was used to detect the pathological morphology in the cerebral cortex of infarcted side of rats. TUNEL staining was used to detect the apoptosis rate of cerebral cortical nerve cells. ELISA was used to detect the contents of interleukin (IL)-1β and IL-18 in the cerebral cortex of infarcted side. Western blot and qPCR were respectively used to detect the protein and mRNA expressions of cGAS, STING, TANK binding kinase-1(TBK1), Interferon regulatory factor 3(IRF3) and NLRP3 in the cerebral cortex of infarcted side.
In comparison with the sham-operation group, the mNSS and the percentage of cerebral infarction were increased (<0.01);there were structural disorders and neuronal damage in the cerebral cortex of infarcted side;the apoptosis rate of nerve cells was increased (<0.01), the contents of IL-1β and IL-18 were increased (<0.01), and the protein and mRNA expressions of cGAS, STING, TBK1, IRF3 and NLRP3 were elevated (<0.01) in the model group. In comparison with the model group, the mNSS and the percentage of cerebral infarction were decreased (<0.01);the pathological damage was alleviated;the apoptosis rate of nerve cells was decreased (<0.01), the contents of IL-1β and IL-18 were decreased (<0.01), and the protein and mRNA expressions of cGAS, STING, TBK1, IRF3 and NLRP3 were reduced (<0.01) in the EA group.
EA can improve cerebral ischemia reperfusion injury, which is related to the inhibition of the cGAS/STING/NLRP3 pathway and inflammatory response in the cerebral cortex.
观察电针（EA）对脑缺血再灌注损伤大鼠大脑皮质环磷酸鸟苷-腺苷酸合成酶（cGAS）/干扰素基因刺激因子（STING）/含NOD样受体家族吡咯结构域蛋白3（NLRP3）通路的影响，探讨EA改善脑缺血再灌注损伤的潜在机制。
将45只SD大鼠随机分为假手术组、模型组和EA组，每组15只。采用改良线栓法建立脑缺血再灌注损伤模型。EA组大鼠于“百会”（GV20）、“风府”（GV16）和“大椎”（GV14）穴进行电针治疗20分钟，每天1次，连续治疗7天。采用改良神经功能缺损评分（mNSS）评估神经功能缺损情况。用TTC染色检测脑梗死面积百分比。用HE染色检测大鼠梗死侧大脑皮质的病理形态。用TUNEL染色检测大脑皮质神经细胞凋亡率。用ELISA检测梗死侧大脑皮质白细胞介素（IL）-1β和IL-18含量。用Western blot和qPCR分别检测梗死侧大脑皮质中cGAS、STING、TANK结合激酶-1（TBK1）、干扰素调节因子3（IRF3）和NLRP3的蛋白和mRNA表达。
与假手术组比较，模型组mNSS评分及脑梗死面积百分比升高（P<0.01）；梗死侧大脑皮质结构紊乱，神经元损伤；神经细胞凋亡率升高（P<0.01），IL-1β和IL-18含量升高（P<0.01），cGAS、STING、TBK1、IRF3和NLRP3的蛋白和mRNA表达上调（P<0.01）。与模型组比较，EA组mNSS评分及脑梗死面积百分比降低（P<0.01）；病理损伤减轻；神经细胞凋亡率降低（P<0.01），IL-1β和IL-18含量降低（P<0.01），cGAS、STING、TBK1、IRF3和NLRP3的蛋白和mRNA表达下调（P<0.01）。
EA可改善脑缺血再灌注损伤，其机制可能与抑制大脑皮质cGAS/STING/NLRP3通路及炎症反应有关。
