Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, People's Republic of China.
Department of Clinical Medicine, Second Military Medical University, Shanghai, 200433, People's Republic of China.
Sci Rep. 2017 Nov 1;7(1):14871. doi: 10.1038/s41598-017-14072-x.
The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H and 33% O) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.
该研究通过高浓度氢气（HCH）的心脏保护作用来研究 Akt1 的作用。C57BL/6 小鼠被随机分为以下几组：假手术组、缺血再灌注组、缺血再灌注+ HCH 组、缺血再灌注+ HCH+LY294002（PI3K 抑制剂）组、缺血再灌注+ HCH+wortmannin（PI3K 抑制剂）组、缺血再灌注+LY294002 组和缺血再灌注+wortmannin 组。在缺血 45 分钟后，在 90 分钟的再灌注期间给予小鼠 HCH（67%H 和 33%O）。为了研究 Akt1 在 HCH 保护作用中的作用，将小鼠分为以下几组：缺血再灌注+A-674563（Akt1 选择性抑制剂）组、缺血再灌注+HCH+A-674563 组、缺血再灌注+CCT128930（Akt2 选择性抑制剂）组和缺血再灌注+HCH+CCT128930 组。在 4 小时再灌注后，进行血清生化、组织学、western blot 和免疫组织化学分析，以评估 PI3K-Akt1 通路在 HCH 保护中的作用。在体外，在 3 小时缺氧后再复氧 4 小时期间给予心肌细胞 75%氢气。进行了几项分析以评估 Akt1 在氢气保护作用中的作用。HCH 导致 Akt1 磷酸化但不导致 Akt2 磷酸化，而 Akt1 抑制则明显消除了 HCH 诱导的心脏保护作用。我们的研究结果表明，HCH 可能通过 PI3K-Akt1 依赖性机制发挥心脏保护作用。
