Zhao Dan, Yin Chen-Yi, Ye Xian-Wei, Wan Zi-Fen, Zhao De-Gang, Zhang Xiang-Yan
Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China.
Life Sciences College of Guizhou University, Guiyang, Guizhou 550025, P.R. China.
Exp Ther Med. 2019 Mar;17(3):2349-2358. doi: 10.3892/etm.2019.7201. Epub 2019 Jan 25.
Obstructive sleep apnoea (OSA) is a very common sleep and breathing disorder that occurs in worldwide. It is important to develop a more effective treatment for OSA to overcome lung cell apoptosis during intermittent hypoxia (IH). A mitochondrial separation protein inhibitor (Mdivi-1) has been demonstrated to be a powerful tool for inhibiting apoptosis. In the present study, the protective effect and possible mechanism of apoptosis in lung cells during IH was investigated using and experiments. Following IH exposure for 4 weeks, the lung tissues of Sprague Dawley rats exhibited interstitial lesions, while Mdivi-1 reduced these pulmonary interstitial lesions. B-cell lymphoma (Bcl)-2 mRNA and protein expression levels were decreased however caspase-3, caspase-9 and dynamin-related protein 1 (Drp-1) mRNA and protein expression levels were increased. Following Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased while caspase-3, caspase-9 and Drp-1 mRNA and protein expression levels were decreased (P<0.05). After exposure to IH for 12 h, the apoptosis rate of WTRL1 cells in rats increased gradually with the IH time (P<0.05). Bcl-2 mRNA and protein expression levels were decreased, whereas caspase-3, caspase-9, cytochrome C (Cyt-C) and Drp-1 mRNA levels were increased, and caspase-3, caspase-9 and Drp-1 protein expression levels were increased. After Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased but caspase-3, caspase-9, Cyt-C and Drp-1 mRNA levels were decreased along with caspase-9, Cyt-C and Drp-1 protein expression levels which were decreased (P<0.05). The results of the present study suggest that Mdivi-1 may be a potential agent for treating OSA because it inhibits the mitochondrial pathway and reduces apoptosis.
阻塞性睡眠呼吸暂停（OSA）是一种非常常见的睡眠和呼吸障碍，在全球范围内都有发生。开发一种更有效的OSA治疗方法以克服间歇性缺氧（IH）期间的肺细胞凋亡很重要。线粒体分离蛋白抑制剂（Mdivi-1）已被证明是一种抑制细胞凋亡的有力工具。在本研究中，使用[具体实验名称1]和[具体实验名称2]实验研究了IH期间肺细胞凋亡的保护作用及可能机制。IH暴露4周后，Sprague Dawley大鼠的肺组织出现间质病变，而Mdivi-1减轻了这些肺间质病变。B细胞淋巴瘤（Bcl）-2 mRNA和蛋白表达水平降低，然而半胱天冬酶-3、半胱天冬酶-9和动力蛋白相关蛋白1（Drp-1）mRNA和蛋白表达水平升高。Mdivi-1干预后，Bcl-2 mRNA和蛋白表达水平升高，而半胱天冬酶-3、半胱天冬酶-9和Drp-1 mRNA和蛋白表达水平降低（P<0.05）。暴露于IH 12小时后，大鼠WTRL1细胞的凋亡率随IH时间逐渐增加（P<0.05）。Bcl-2 mRNA和蛋白表达水平降低，而半胱天冬酶-3、半胱天冬酶-9、细胞色素C（Cyt-C）和Drp-1 mRNA水平升高，半胱天冬酶-3、半胱天冬酶-9和Drp-1蛋白表达水平升高。Mdivi-1干预后，Bcl-2 mRNA和蛋白表达水平升高，但半胱天冬酶-3、半胱天冬酶-9、Cyt-C和Drp-1 mRNA水平降低，同时半胱天冬酶-9、Cyt-C和Drp-1蛋白表达水平降低（P<0.05）。本研究结果表明，Mdivi-1可能是一种治疗OSA的潜在药物，因为它抑制线粒体途径并减少细胞凋亡。
