摘要
心肌缺血再灌注损伤(MIRI)是指由于一些原因导致心肌细胞缺血性损伤,然而在恢复血液供应后心肌细胞损伤进一步加重,从而引发再灌注性心律失常、心肌顿抑、微循环障碍和血液无复流等现象,是临床治疗中亟待解决的问题。因此,探索如何改善MIRI具有重要的临床意义。磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路被认为是预防MIRI的重要级联信号通路,串扰在氧化应激、钙超载、自噬、炎症、内质网应激和线粒体障碍等多种机制中,并处于核心位点,与MIRI的严重程度密切相关。同时,中医药凭借其多靶点、多通路和毒副作用小的优势以及中医的辨证治疗、整体观念等特点,使其在防治MIRI方面有着独特的优势。大量研究已证实,该通路是众多中药复方、中药单体以及中药提取物常见的作用机制。因此,本文将阐述PI3K/Akt信号通路串扰在MIRI机制中的作用,重点对PI3K/Akt信号通路关键靶标与MIRI的关系进行综述,以便深刻理解其中错综复杂的关系,促进针对PI3K/Akt信号通路的新型药物的研发。最后总结中医药对该通路已有的研究成果,为MIRI的治疗及药物研发提供参考依据。
Myocardial ischemia-reperfusion injury(MIRI)was originated from the ischemic injury to myocardial cells due to some factors,and the injury will be aggravated after the blood supply recovery.MIRI will cause reperfusion arrhythmia,myocardial stagnation,microcirculation disorders or blood loss reflow,and become a key issue to be solved in the clinical treatment.Therefore,it is of important clinical significance to explore how to improve MIRI.The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway has been regarded to be an important cascade signaling pathway to prevent MIRI,which is cross-talked in such mechanisms as oxidative stress,calcium overload,autophagy,inflammation,endoplasmic reticulum stress and mitochondrial dysfunction.This pathway is at the core site and closely related to the severity of MIRI.Meanwhile,traditional Chinese medicine(TCM)has its unique advantages in the prevention and treatment of MIRI,including multiple targets,multiple pathways,fewer toxic and side effect,as well as TCM characteristics of syndrome differentiation treatment and overall concept.A great number of studies have confirmed that this pathway is a common mechanism of action for most TCM compounds,TCM monomers and extracts.In this paper,we clarify the effect of PI3K/Akt signaling pathway crosstalk on the myocardial ischemia-reperfusion injury,with the focus on the relationship between the key targets of PI3K/Akt signaling pathway and MIRI.It will give great insights to the intricate relationship between them and promote the future development of new drugs targeting the PI3K/Akt signaling pathway.Finally,we also summarized the existing findings of TCM on PI3K/Akt pathway,which provides a reference for the treatment and drug development of MIRI.
作者
谢延峥
马金
邹旭
XIE Yan-zheng;MA Jin;ZOU Xu(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong 510000,China;Guangdong Provincial Key laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases Guangzhou,Guangdong 510000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第24期201-210,共10页
Chinese Journal of Experimental Traditional Medical Formulae
基金
广东省财政厅项目(粤财工(2016)150号)
广东省中医药局项目(粤中医办函(2020)1号)
广东省中医院中医学术流派传承工作室建设项目(中医二院(2013)233号)
广东省中医院中医药科学技术研究专项(YN2019MJ10,YN2018MJ02)
广东省基础与应用基础研究基金联合基金-重点项目(2019B1515120040)
广东省自然科学基金项目(2019A1515010808)。
