Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong 510100, P.R. China.
Department of Bioinformatics, Guangzhou GenCoding Lab, Guangzhou, Guangdong 510670, P.R. China.
Mol Med Rep. 2018 Oct;18(4):3547-3554. doi: 10.3892/mmr.2018.9375. Epub 2018 Aug 9.
Hypoxia‑ischemia (H‑I) is frequently observed in perinatal asphyxia and other diseases. It can lead to serious cardiac injury, cerebral damage, neurological disability and mortality. Previous studies have demonstrated that the phosphatidylinositol‑3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which regulates a wide range of cellular functions, is involved in the resistance response to H‑I through the activation of proteins associated with survival and inactivation of apoptosis‑associated proteins. It can also regulate the expression of hypoxia‑induced factor‑1α (HIF‑1α). HIF‑1α can further regulate the expression of downstream proteins involved in glucose metabolism and angiogenesis, such as vascular endothelial growth factor and erythropoietin, to facilitate ischemic adaptation. Notably, HIF‑1α may also induce detrimental effects. The effects of HIF‑1 on ischemic outcomes may be dependent on the H‑I duration, animal age and species. Thus, further investigation of the PI3K/Akt signaling pathway may provide further insights of the potential targets for treating diseases accompanied by H‑I.
缺氧缺血（H-I）在围产期窒息和其他疾病中经常观察到。它可导致严重的心脏损伤、脑损伤、神经功能障碍和死亡率。先前的研究表明，调节广泛的细胞功能的磷脂酰肌醇 3 激酶（PI3K）/蛋白激酶 B（Akt）信号通路通过激活与生存相关的蛋白和失活凋亡相关蛋白参与对 H-I 的抵抗反应。它还可以调节缺氧诱导因子-1α（HIF-1α）的表达。HIF-1α 可以进一步调节参与葡萄糖代谢和血管生成的下游蛋白的表达，如血管内皮生长因子和促红细胞生成素，以促进缺血适应。值得注意的是，HIF-1α 也可能产生有害影响。HIF-1 对缺血性结果的影响可能取决于 H-I 的持续时间、动物年龄和物种。因此，进一步研究 PI3K/Akt 信号通路可能为治疗伴有 H-I 的疾病提供更多的潜在靶点。
