Government College University, Faisalabad, Pakistan.
Government College University, Faisalabad, Pakistan.
Prostaglandins Other Lipid Mediat. 2020 Aug;149:106436. doi: 10.1016/j.prostaglandins.2020.106436. Epub 2020 Mar 12.
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.
缺血再灌注损伤是一种复杂的血液动力学病理现象，涉及代谢到炎症机制在心力衰竭、中风和急性肾衰竭等疾病的发展。尽管有大量的研究有助于了解其发病机制，但针对缺血再灌注损伤的靶向治疗方法仍然至关重要。缺血或药物处理一直是利用内源性保护机制对抗缺血再灌注损伤的长期确立的操作，这促进了潜在治疗靶点的发展，如鞘脂信号。1-磷酸鞘氨醇已成为鞘脂调节细胞存活、血管完整性和缺血再灌注损伤中炎症级联反应的关键代谢物。1-磷酸鞘氨醇信号转导过程被认为可以降低线粒体功能障碍、凋亡组装以及上调 RISK 和 SAFE 生存途径。它还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。针对这种单一物质的信号转导具有广泛影响缺血再灌注损伤有害信号转导的巨大潜力。本综述强调了 S1P 信号转导的作用和意义，该信号转导可以被治疗性利用来治疗不同器官的缺血再灌注损伤介导的病理状况。
