Zheng Xiao-Bin, Wang Chao, Zhang Ming, Yao Bing-Qi, Wu Hai-Yan, Hou Shu-Xian
Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan City, 030000, China.
Sleep Breath. 2024 Dec 3;29(1):43. doi: 10.1007/s11325-024-03216-9.
Hydrogen sulfide (HS) is a novel gas signaling molecule that has been researched in several physiological and pathological conditions, indicating that strategies targeting HS may provide clinical benefits in diseases such as chronic cardiomyopathy. Here, we reveal the effect of HS on chronic intermittent hypoxia (CIH)-related myocardial damage and its mechanistic relevance to phosphoinositol-3 kinase (PI3K).
Mice were subjected to a 4-week CIH process to induce myocardial damage, which was accompanied by daily administration of NaHS (a HS donor) and LY294002 (an inhibitor of PI3K). Changes in heart function were evaluated via echocardiography. Histological examination was applied to assess heart tissue lesions. Myocardial apoptosis was detected by TUNEL staining and apoptosis-associated protein expression. Furthermore, the effects of NaHS on autophagy and the PI3K/AKT/mTOR pathway were investigated. Finally, the level of inflammation is also affected by related proteins.
The CIH group presented increased myocardial dysfunction and heart tissue lesions. Echocardiography and histological analysis revealed that, compared with control mice, CIH-treated mice presented significantly more severe left ventricular remodeling and decreased myocardial contractile function. In addition, the apoptosis index and oxidative markers were significantly elevated in the CIH group compared with those in the control group. The autophagy marker Beclin-1 was decreased, while p62 was elevated by CIH treatment. HS supplementation with NaHS significantly improved cardiac function and alleviated fibrosis, oxidative stress, and apoptosis but upregulated autophagy in CIH mice, and these effects were also observed in animals that underwent only PI3K blockade. Furthermore, PI3K/AKT pathway-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway, the Nrf2/HO-1 pathway and proinflammatory NF-κB activity were shown to play a role in the therapeutic effect of NaHS after CIH stimulation.
硫化氢（HS）是一种新型气体信号分子，已在多种生理和病理条件下进行了研究，这表明针对HS的策略可能为慢性心肌病等疾病带来临床益处。在此，我们揭示了HS对慢性间歇性缺氧（CIH）相关心肌损伤的影响及其与磷酸肌醇-3激酶（PI3K）的机制相关性。
小鼠接受为期4周的CIH过程以诱导心肌损伤，在此期间每天给予硫氢化钠（NaHS，一种HS供体）和LY294002（一种PI3K抑制剂）。通过超声心动图评估心脏功能的变化。应用组织学检查来评估心脏组织损伤。通过TUNEL染色和凋亡相关蛋白表达检测心肌细胞凋亡。此外，研究了NaHS对自噬以及PI3K/AKT/mTOR通路的影响。最后，炎症水平也受到相关蛋白的影响。
CIH组出现心肌功能障碍和心脏组织损伤增加。超声心动图和组织学分析显示，与对照小鼠相比，CIH处理的小鼠左心室重构明显更严重，心肌收缩功能降低。此外，与对照组相比，CIH组的凋亡指数和氧化标志物显著升高。CIH处理使自噬标志物Beclin-1降低，而p62升高。用NaHS补充HS可显著改善CIH小鼠的心脏功能，减轻纤维化、氧化应激和细胞凋亡，但上调自噬，并且在仅接受PI3K阻断的动物中也观察到了这些作用。此外，PI3K/AKT通路介导的对哺乳动物雷帕霉素靶蛋白（mTOR）通路、Nrf2/HO-1通路和促炎NF-κB活性的抑制在CIH刺激后NaHS的治疗作用中发挥了作用。
