Department of Histology& Embryology, Basic Medicine School, Dali University, Yunnan, China.
Department of Rehabilitation, Jinshan Hospital, Fudan University, Shanghai, China.
Metab Brain Dis. 2019 Oct;34(5):1299-1311. doi: 10.1007/s11011-019-00450-z. Epub 2019 Jun 20.
It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.
众所周知，在缺血性缺氧中，缺氧诱导因子-1α（HIF-1α）在触发其下游靶基因表达方面起着关键作用，产生多种产物，如促红细胞生成素（EPO）、血管内皮生长因子（VEGF）、一氧化氮合酶（NOS）、葡萄糖转运蛋白-1（GLUT-1）、胰岛素样生长因子（IGF），进一步促进红细胞生成、血管生成、血管扩张和葡萄糖资本化以克服缺氧。同时，作为对血管具有相反作用的因素，内皮素-1（ET-1）和脑钠肽（BNP）在缺血性病理生理学中也非常突出。时至今日，已经使用了几种预处理方式来诱导对缺血的耐受性。在我们的研究中，应用了运动预处理，结果表明 HIF-1α 触发了 ET-1 和 BNP 的表达，这证实了它们是 HIF-1α 的下游靶基因。并且 ET-1 可能在某种程度上影响 BNP 的表达，但不是调节 BNP 表达的唯一因素。因此，我们的研究结果表明，运动预处理可能通过 HIF-1α 为缺血性脑组织提供保护，进而增加 BNP 的表达，与 VEGF 和 EPO 等其他因素协同作用，增加缺血区域的血流量，从而减轻缺血引起的损伤。
