循经取穴调控HMGB1/RAGE/cathepsinB信号通路抑制心肌缺血再灌注细胞焦亡的机制研究

心肌缺血再灌注损伤（MIRI）是导致心肌梗死面积扩大、恶性心律失常甚至猝死的重要病理机制。心肌细胞焦亡是加重MIRI炎症反应的主因，活化NLRP3炎症小体是焦亡启动前提。最新研究发现，高迁移率族蛋白B1（HMGB1）及其受体RAGE、cathepsinB组成的信号通路可活化NLRP3炎症小体。课题组前期临床研究证实循经取穴针刺内关穴可显著改善冠心病患者心绞痛频率和程度。预实验证实针刺内关穴可抑制MIRI细胞焦亡，机制仍需深入研究。故提出假说：针刺内关穴后处理可调控HMGB1/RAGE/cathepsinB信号通路介导的NLRP3炎症小体活化，抑制细胞焦亡，抗MIRI。本项目以大鼠MIRI模型为研究对象，以HMGB1/RAGE/cathepsinB信号通路，NLRP3炎症小体及焦亡途径为切入点，探讨针刺内关穴后处理抗MIRI分子机制，为丰富循经取穴理论及临床应用针刺抗MIRI提供新思路。

Myocardial ischemia-reperfusion injury (MIRI) is an important pathological mechanism leading to the expansion of myocardial infarction area, malignant arrhythmia and even sudden death. Myocyte pyroptosis is the main cause to aggravate MIRI inflammatory response. Activation of NLRP3 inflammasome is the premise of pyroptosis initiation. Recent studies have found that signaling pathways composed of high mobility group protein B1(HMGB1) and its receptors RAGE and cathepsinB could activate NLRP3 inflammasome. Clinical study of the research group has confirmed that acupuncturing at Neiguan (PC6) points along the meridian can significantly alleviate the frequency and degree of angina pectoris in patients with coronary heart disease. Preliminary experimental results showed that post-treatment of acupuncturing at PC6 point can inhibit the myocyte pyroptosis in MIRI. Therefore, hypothesis is as follows: post-treatment of acupuncturing at PC6 point can regulate HMGB1/RAGE/.cathepsinB signaling pathway to activate NLRP3 inflammasome to inhibit myocyte pyroptosis and treat MIRI. This project is going to take the rat MIRI model as the research object, focusing on HMGB1/RAGE/cathepsinB signal pathway, NLRP3 inflammasome and myocyte pyroptosis. It will explore the molecular mechanism of post-treatment of acupuncturing at PC6 point in treating MIRI, provide new idea for enriching the meridian theory and provide a new clinical idea for acupuncture treatment of MIRI.