Ischemia and reperfusion injury is a complex hemodynamic pathological phenomenon that engages the metabolic to inflammatory machinery in development of disease conditions like heart failure, stroke and acute kidney failure. Target specific therapeutic approaches for ischemia reperfusion injury remains critical despite the extensive studies contributing to the understanding of its pathogenesis. Ischemic or pharmacological conditionings have been long established manipulations to harness the endogenous protective mechanisms against ischemia reperfusion injury that fostered the development of potential therapeutic targets such as sphingolipids signaling. Sphingosine 1-phosphate has been emerged as a crucial metabolite of sphingolipids to regulate the cell survival, vascular integrity and inflammatory cascades in ischemia reperfusion injury. Sphingosine 1-phosphate signaling process has been implicated to downgrade the mitochondrial dysfunction, apoptotic assembly along with upregulation of RISK and SAFE pro-survival pathways. It also regulates the endothelial dysfunction and immune cells behavior to control the vascular permeability and immune cells infiltration at ischemia reperfusion injury site. Targeting the signaling of this single moiety holds the vast potential to extensively influence the detrimental signaling of ischemia reperfusion injury. This review highlights the role and significance of S1P signaling that can be therapeutically exploit to treat ischemia reperfusion injury mediated pathological conditions in different organs.

中文翻译：

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鞘氨醇1-磷酸信号在缺血和再灌注损伤中的作用。

缺血和再灌注损伤是一种复杂的血液动力学病理现象，在心力衰竭，中风和急性肾衰竭等疾病的发展过程中，新陈代谢与炎症机制有关。尽管进行了广泛的研究有助于了解其发病机理，但针对缺血再灌注损伤的靶标特异性治疗方法仍然至关重要。长期以来，缺血或药理条件已被确立，以利用针对缺血性再灌注损伤的内源性保护机制，这种机制促进了潜在治疗靶标如鞘脂信号的发展。1-磷酸鞘氨醇已成为鞘脂的重要代谢产物，可调节缺血再灌注损伤中的细胞存活，血管完整性和炎症级联反应。鞘氨醇1-磷酸信号传递过程已被证明可降低线粒体功能障碍，凋亡组装以及RISK和SAFE促存活途径的上调。它还可调节内皮功能障碍和免疫细胞行为，以控制缺血再灌注损伤部位的血管通透性和免疫细胞浸润。靶向该单一部分的信号传导具有巨大的潜力，可以广泛地影响缺血再灌注损伤的有害信号传导。这篇综述强调了S1P信号传导的作用和意义，可以在治疗上利用它来治疗缺血再灌注损伤介导的不同器官的病理状况。凋亡组装以及RISK和SAFE促存活途径的上调。它还可调节内皮功能障碍和免疫细胞行为，以控制缺血再灌注损伤部位的血管通透性和免疫细胞浸润。靶向该单一部分的信号传导拥有巨大的潜力，可以广泛影响缺血再灌注损伤的有害信号传导。这篇综述强调了S1P信号传导的作用和意义，可以在治疗上利用它来治疗缺血再灌注损伤介导的不同器官的病理状况。凋亡组装以及RISK和SAFE促存活途径的上调。它还可调节内皮功能障碍和免疫细胞行为，以控制缺血再灌注损伤部位的血管通透性和免疫细胞浸润。靶向该单一部分的信号传导拥有巨大的潜力，可以广泛影响缺血再灌注损伤的有害信号传导。这篇综述强调了S1P信号传导的作用和意义，可以在治疗上利用它来治疗缺血再灌注损伤介导的不同器官的病理状况。靶向该单一部分的信号传导拥有巨大的潜力，可以广泛影响缺血再灌注损伤的有害信号传导。这篇综述强调了S1P信号传导的作用和意义，可以在治疗上利用它来治疗缺血再灌注损伤介导的不同器官的病理状况。靶向该单一部分的信号传导拥有巨大的潜力，可以广泛影响缺血再灌注损伤的有害信号传导。这篇综述强调了S1P信号传导的作用和意义，可以在治疗上利用它来治疗缺血再灌注损伤介导的不同器官的病理状况。