缺血预处理和后处理减轻缺血/再灌注损伤的分子机制

Molecular mechanisms of ischaemic pre-and post-conditioning attenuating ischemia/reperfusion injury

背景 组织长时间缺血后再灌注能导致缺血/再灌注（ischaemia/reperfusion,I/R）损伤.研究证实缺血预处理和缺血后处理可减轻I/R损伤大约75％. 目的 综述缺血预处理和缺血后处理减轻I/R损伤的分子机制. 内容 缺血预处理和缺血后处理的分子机制涉及腺苷、缓激肽、阿片和大麻素激活的细胞表面G耦联蛋白受体.这些物质依次兴奋生长受体,继而激活细胞保护性通路,其中包括通过有丝分裂原激活蛋白激酶（mitogen-activated protein kinase,MEK）/细胞外信号调节激酶1/2（extracellular signal-regular kinase 1/2,ERK1/2）途径减少细胞凋亡以及通过磷脂酰肌醇-3激酶途径减少线粒体通透性转换孔（mitochondrial permeability transition pore,mPTP）开放.mPTp开放能够导致细胞死亡.最近研究提示,细胞表面激活的肿瘤坏死因子-α受体通过激活Janus激酶以及信号转导子和转录激活因子3途径而发挥细胞保护作用. 趋向 缺血预处理和缺血后处理减轻I/R损伤的分子机制目前仍在研究中,有望在对此更深入理解的基础上获得可转化为有意义的临床治疗措施.

Background Reperfusion of tissues subjected to prolonged ischaemia can results in ischemia/reperfusion（I/R） injury.It has been shown that ischemic pre-and post-conditioning can reduce I/R injury about 75%.Objective To review molecular mechanisms of ischaemic pre-and post-conditioning attenuating I/R injury.Content The molecular mechanisms of ischaemic pre-and post-conditioning attenuating I/R injury involve the activation of surface G-protein-coupled receptors for adenosine,bradykinin,opioids,and cannabinoids.These in turn stimulate growth receptors which then trigger the activation of cytoprotective pathways resulting in a reduction in apoptosis via the mitogen-activated protein kinase（MEK）/extracellular-signal regulated kinase 1/2 （ERK1/2） route and a reduction in opening of mitochondrial permeability transition pores via the phosphatidylinositol 3-kinase pathway.Opening of mitochondrial permeability transition pores （mPTP） can cause cell death.The recent studies indicate that activated surface tumor necrosis factor-α receptors also contribute to cytoprotection by activating the Janus kinase and the signal transducer and activating factor of transcription-3 pathway.Trend The studies regarding molecular mechanisms of ischaemic preand post-conditioning attenuating I/R injury is still ongoing.It is hope that with the better understanding of these interventional strategies,possible translation into meaningful clinical therapies will be developed.