基于自噬-炎症调控的电针预处理减轻心肌IR损伤的mTOR/NLRP3信号机制研究

Our previous studies showed that electro-acupuncture（EA） preconditioning at different time alleviates myocardial ischemia-reperfusion injury (MIRI) , which are all related to autophagy, and reduces the expression of inflammatory substances at the same time. Considering the fact that inflammatory response which accompanies the whole course of MIRI, determines process and prognosis, we propose the hypothesis that " it is an important mechanism for electro-acupuncture preconditioning against MIRI via mTOR/NLRP3 signals mediated autophagy-inflammation crosstalk ".In this study, we used MIRI rats as carriers to explore the cascade process of autophagy-inflammation crosstalk of EA promoting myocardial protection on the basis of fully evaluating the effect of EA against MIRI by using echocardiography, electron microscopy, immunofluorescence, enzyme-linked immunosorbent assay, RealTime-PCR, WB, in vivo target blocking technology, etc, in order to reveal the cascade mechanism of “electro-acupuncture preconditioning-- inhibiting mTOR expression and promoting autophagy--reducing mitochondrial damage-- inhibiting NLRP3 inflammasome-- inhibiting inflammatory response-- reducing cardiomyocyte pyroptosis-- promoting MIRI protection” fully, and in the meantime, to reveal the protective mechanism of electro-acupuncture preconditioning for MIRI, provide scientific evidence for its clinical transformation and application, enrich the scientific connotation of acupuncture for disease prevention, and speed up the better integration of acupuncture into the era of great health.

基于前期研究新发现：不同时间窗电针预处理减轻心肌缺血再灌注损伤（MIRI）效应都与自噬相关，且同时降低炎症物质表达；结合炎性反应伴随MIRI全程，并决定其进程和预后，以及mTOR/NLRP3介导自噬-炎症调控的新前沿，我们率先提出“mTOR/NLRP3信号介导的自噬-炎症调控是电针预处理减轻MIRI的重要机制”假说，在中医针灸理论指导下，以MIRI大鼠为载体，采用超声心动图、电镜、免疫荧光、酶联免疫、qPCR、WB等分子生物学技术，并结合在体靶标阻断技术，在充分评价效应的基础上，深入探索电针促心肌保护的自噬-炎症调控级联效应过程，以期全面揭示“电针预处理—抑制mTOR表达，促进自噬—减少线粒体损伤—抑制NLRP3介导的炎性反应—减少心肌细胞焦亡—促进MIRI保护”效应级联机制，为电针预处理保护MIRI的临床转化和应用提供实验证据，丰富针灸治未病的科学内涵，加快针灸医学更好地融入大健康时代。