Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Department of Rehabilitation, Elderly Rehabilitation Hospital, Suzhou Red Cross Society, Suzhou, Jiangsu 215009, P.R. China.
Mol Med Rep. 2020 Sep;22(3):1759-1766. doi: 10.3892/mmr.2020.11291. Epub 2020 Jun 30.
Diabetes mellitus (DM) facilitates atrial fibrosis and increases the risk of atrial fibrillation (AF). The underlying mechanism of DM in causing AF remains mostly unknown and potential therapeutic targets for DM‑induced AF are rarely reported. Hydrogen sulfide (H2S) has drawn considerable attention in recent years for its potential as a cardiovascular protector. Thus, the aim of the present study was to investigate the effect of H2S on DM‑induced AF and the mechanism of action. Sprague‑Dawley rats were divided into four groups, including the control group, the DM group, the H2S group and the DM+H2S group. The DM group and the DM+H2S group were administered streptozotocin to induce DM, whereas the other two groups were given citrate buffer as a control. The H2S group and the DM+H2S group were administered with an intraperitoneal injection of sodium hydrosulfide (precursor of H2S). AF inducibility, AF duration, atrial fibrosis and vital protein expression of oxidative stress were compared among the four groups. The DM group showed significantly higher AF incidence rates and duration (P<0.05). Histology results demonstrated severe atrial fibrosis in the DM group, and the PI3K/Akt/endothelial nitric oxide synthase (eNOS) pathway was significantly downregulated (P<0.05). However, when H2S was administered, the rats showed lower AF incidence and duration compared with the DM group. Additionally, H2S was able to mitigate the atrial fibrosis induced by DM, as well as the proliferation and migration of cardiac fibroblasts, as demonstrated by an MTT assay and real‑time cell analyzer migration experiment. Western blotting showed that the expression levels of the PI3K/Akt/eNOS pathway in the DM+H2S group were significantly upregulated compared with those of the DM group (P<0.05). In summary, DM status can lead to the structural remodeling of atrial fibrosis, facilitating AF incidence and persistence. Administration of H2S does not affect the glucose level, but can significantly mitigate atrial fibrosis and reduce the incidence of AF induced by DM, probably via activation of the PI3K/Akt/eNOS pathway.
糖尿病（DM）可促进心房纤维化并增加心房颤动（AF）的风险。DM 导致 AF 的潜在机制在很大程度上尚不清楚，很少有报道潜在的 DM 诱导 AF 的治疗靶点。近年来，由于其作为心血管保护剂的潜力，硫化氢（H2S）引起了相当大的关注。因此，本研究旨在探讨 H2S 对 DM 诱导的 AF 的影响及其作用机制。将 Sprague-Dawley 大鼠分为四组，包括对照组、DM 组、H2S 组和 DM+H2S 组。DM 组和 DM+H2S 组给予链脲佐菌素诱导 DM，而其他两组给予柠檬酸盐缓冲液作为对照。H2S 组和 DM+H2S 组给予腹腔内注射硫氢化钠（H2S 的前体）。比较四组之间的 AF 易感性、AF 持续时间、心房纤维化和氧化应激关键蛋白表达。DM 组 AF 发生率和持续时间明显升高（P<0.05）。组织学结果显示 DM 组心房纤维化严重，PI3K/Akt/内皮型一氧化氮合酶（eNOS）通路明显下调（P<0.05）。然而，当给予 H2S 时，与 DM 组相比，大鼠的 AF 发生率和持续时间较低。此外，H2S 能够减轻 DM 诱导的心房纤维化，以及 MTT 测定和实时细胞分析迁移实验表明的心肌成纤维细胞的增殖和迁移。Western blot 显示 DM+H2S 组的 PI3K/Akt/eNOS 通路表达水平明显高于 DM 组（P<0.05）。综上所述，DM 状态可导致心房纤维化的结构重塑，促进 AF 的发生和持续。给予 H2S 不影响血糖水平，但可显著减轻 DM 诱导的心房纤维化，降低 AF 的发生率，可能通过激活 PI3K/Akt/eNOS 通路。
