中文摘要
自噬在心肌IR损伤中担当重要作用,通过促进适度自噬、避免过度自噬,调节自噬稳态来减轻IRI,是当前研究重点。AMPK-mTOR1-ULK1及Akt-Bcl2-Beclin1信号通路是心肌IR过程中调节自噬反应的重要途径。研究证实,不同时期的针灸介入,均存在一定程度的抗IRI作用,然而其效应差异及具体机制尚未明确。本研究以心肌IRI模型大鼠为载体,在通过血清酶谱、心肌细胞凋亡、心肌细胞结构检测等方法评价效应的基础上,以电镜观察自噬小体,免疫组化、WB、qPCR等技术观察凋亡基因Bax/Bcl2,AMPK-mTOR1-ULK1及Akt-Bcl2-Beclin1信号通路表达,比较不同时间窗电针干预抗IRI的效应差异,并从AMPK-mTOR1-ULK1及AKt-Bcl2-Beclin1信号通路,探讨电针抗IRI的自噬相关机制,为其抗IRI提供理论依据,也为临床抗IRI针刺介入治疗的时间窗提供依据。
英文摘要
Myocardial ischemia and reperfusion (I/R) can cause reperfusion injury (IRI) and how to reduce IRI is of great significance during myocardial recovery. Autophagy plays an important role in I/R process and the regulation of autophagy homeostasis by promoting moderate autophagy, avoiding excessive autophagy is the focus of modern research. AMPK-mTOR1-ULK1 and Akt-Bcl2-Beclin1 signaling pathway are important pathways for the regulation of autophagy in the process of myocardial I/R. The researches confirmed that acupuncture treatment in different stages of I/R have certain anti-IRI effect, but the difference of the effect and the mechanism is not clear. In this study, the rat model of myocardial ischemia was used to compare the different effects of electroacupuncture at different stages on IRI and explore the mechanism of autophagy from AMPK-mTOR1-ULK1 and AKt-Bcl2-Beclin1 signaling pathway, by serum enzyme, myocardial cell apoptosis and myocardial cell structure detection to evaluate the electroacupuncture effect ,electron microscopic to observe autophagy body and Immunohistochemistry, WB, qPCR to observe the expression of apoptosis gene Bax/Bcl2, mTOR1-ULK1-AMPK and Akt-Bcl2-Beclin1 signaling pathway. And in the meantime,to provide evidence for the time window of interventional treatment of acupuncture anti IRI.
