IKK/NF-κB及PI3K-Akt信号转导通路在MI/RI过程中对心肌细胞的自噬反应发挥着正负两种调控作用，可同时促进/抑制自噬发生，且两条通路间又具有彼此作用的交互节点。因而，能否通过影响P13K/Akt-IKK/NF-κB网络中的关键作用点而使这两条信号通路在MI/RI自噬反应过程中发挥协同保护作用，对于MI/RI机制及防治研究具有重要作用。本研究以PI3K/Akt-IKK/NF-κB信号转导网络与MI/RI过程自噬间交互作用为切入点，在明确自噬对MI/RI心肌损伤/保护作用的基础上，进一步阐明PI3K/Akt、IKK/NF-κB信号通路间的交互作用及其对自噬的影响；同时以痰瘀同治方为干预手段，并与活血化瘀方和化痰散结方进行对比观察，研究该方对自噬、PI3K/Akt-IKK/NF-κB信号转导网络系统的具体调节位点和作用优势，力求从新的角度阐释痰瘀同治法对MI/RI的防治作用机理。

In the process of MI/RI ，IKK/NF-κB and PI3K-Akt signal transduction pathways influence the autophagic response of myocardial cells through the positive and negative regulation. There are some interactive node interactions between the two pathways ，so they can promote or inhibit autophagy simultaneously. It's important for prevention and treatment of MI/RI through affectting the key role of P13K/Akt-IKK/NF-κB network and concerting the two signal pathways playing synergetic protective effect on autophagy in MI/RI. This research focus on the interaction between PI3K/Akt-IKK/NF-κB signal transduction network and autophagy ,clear the protective or injurious effect on MI/RI and further studies interaction between PI3K/Akt and IKK/NF-κB signal pathways and its effect on autophagy. Moreover,the therapy with phlegm and blood stasis resolved simultaneously will be the means of intervention, at the same time with the removing phlegm and enlarging chest method and activating blood and dissolving stasis method for comparative observation. The accommodation mechanism will be revealed partly from a new point of view through observing the effect of the treatment on the specific sites of P13K/Akt-IKK/NF-κB signal transduction network and autophagy in the process of MI/RI.

IKK/NF-κB及PI3K-Akt信号转导通路在MI/RI过程中对心肌细胞的自噬反应发挥着正负两种调控作用，能否通过调控这两条信号通路并在MI/RI自噬反应过程中发挥协同保护作用，对于MI/RI机制及防治研究具有重要作用。本研究以PI3K/Akt-IKK/NF-κB信号转导网络与MI/RI过程自噬间交互作用为切入点，在明确自噬对MI/RI心肌损伤/保护作用的基础上，再进一步阐明PI3K/Akt、IKK/NF-κB信号通路对自噬的影响；同时以痰瘀同治方为干预手段，并与活血化瘀方和化痰散结方进行对比观察，揭示该方对自噬、PI3K/Akt-IKK/NF-κB信号转导网络系统的具体调节位点和作用优势。本研究证实自噬在心肌缺血时被诱发，再灌注期得到进一步加强。虽然缺血诱发的自噬对心肌有一定保护作用，但在再灌注阶段自噬的加强可加重心肌损伤。痰瘀同治方可通过上调MI/RI心肌PI3K，p-Akt蛋白水平、抑制IKKβ、NF-κBp65蛋白高表达而起到激活PI3K-Akt通路，并抑制IKK/NF-κB通路活化，减轻自噬性损伤的作用。研究同时观察了痰瘀同治方对AMPK/mTOR通路的作用机制，体外实验显示痰瘀同治方可通过抑制H/R心肌细胞AMPK活化并促进mTOR表达来调控AMPK/mTOR通路。总之，痰瘀同治方可通过调节IKK/NF-κB，PI3K/Akt，AMPK/mTOR多条信号通路，而起到减少心肌酶释放，抑制细胞凋亡，减轻自噬反应抗自噬过表达的综合保护作用。