Qiu Zhengguo, Ma Jianbing, Zhang Xiaqing, Jiao Mingna, Zhi Liqiang
Department of Anesthesiology, Banan Hospital of Chongqing Medical University, Chongqing, PR China.
Department of Joint, Honghui Hospital, Xi'an Jiaotong University, No.555 Youyi East Road, Xi'an, Shaanxi 710054, PR China.
Brain Res Bull. 2025 Feb;221:111200. doi: 10.1016/j.brainresbull.2025.111200. Epub 2025 Jan 7.
Electroacupuncture (EA) and trigonelline (TG) have been reported to be beneficial in alleviating cerebral ischemia/reperfusion injury (CIRI). However, the synergistic effects of EA and TG in CIRI and the underlying mechanism have not been demonstrated.
Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and reperfusion (MCAO/R) to establish a CIRI model. Neurological deficit score was evaluated using Garcia's scale. Cerebral infarction in rats was determined using TTC staining. Brain tissue morphology was assessed by HE staining. The expression of various proteins was measured using IF assay and western blot.
EA or TG treatment could effectively ameliorate neurological disorders, attenuate cerebral infarction and reduce neuronal damage in brain tissue in CIRI rats. In addition, EA or TG treatment suppressed autophagy and pyroptosis in CIRI rats. More importantly, synergistic effects of EA and TG intervention in CIRI rats were observed in ameliorating neuronal damage and suppressing autophagy and pyroptosis, while Rapa, an inducer of autophagy, strengthened these effects in MCAO/R-induced rats. Furthermore. Rapa reversed EA in combination with TG-mediated improvement of neuronal damage and suppression of autophagy and pyroptosis in CIRI rats. Notably, the PI3K/AKT/mTOR pathway was inactivated in CIRI rats and EA combined with TG enhanced the activation of the PI3K/AKT/mTOR pathway. LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, stimulated autophagy and pyroptosis in CIRI rats and reversed EA combined with TG-mediated suppression of autophagy and pyroptosis.
EA combined with TG suppressed pyroptosis, which was dependent on inhibition of autophagy in CIRI rats through activation of the PI3K/AKT/mTOR signaling pathway.
据报道，电针（EA）和胡芦巴碱（TG）对减轻脑缺血/再灌注损伤（CIRI）有益。然而，EA和TG在CIRI中的协同作用及其潜在机制尚未得到证实。
对大鼠进行大脑中动脉闭塞（MCAO）手术及再灌注（MCAO/R）以建立CIRI模型。使用Garcia评分评估神经功能缺损评分。通过TTC染色确定大鼠脑梗死情况。采用HE染色评估脑组织形态。使用免疫荧光分析（IF）和蛋白质免疫印迹法检测各种蛋白质的表达。
EA或TG治疗可有效改善CIRI大鼠的神经功能障碍，减轻脑梗死并减少脑组织中的神经元损伤。此外，EA或TG治疗可抑制CIRI大鼠的自噬和焦亡。更重要的是，观察到EA和TG干预对CIRI大鼠在改善神经元损伤以及抑制自噬和焦亡方面具有协同作用，而自噬诱导剂雷帕霉素（Rapa）在MCAO/R诱导的大鼠中增强了这些作用。此外，Rapa逆转了EA联合TG介导的CIRI大鼠神经元损伤改善以及自噬和焦亡抑制。值得注意的是，PI3K/AKT/mTOR通路在CIRI大鼠中失活，EA联合TG增强了PI3K/AKT/mTOR通路的激活。PI3K/AKT/mTOR通路抑制剂LY294002刺激CIRI大鼠的自噬和焦亡，并逆转EA联合TG介导的自噬和焦亡抑制。
EA联合TG抑制焦亡，这依赖于通过激活PI3K/AKT/mTOR信号通路抑制CIRI大鼠的自噬。
