{"title":"外源性H2S靶向PI3K/AKT/mTOR通路，通过抑制氧化应激和增强自噬，缓解慢性间歇性缺氧引起的心肌损伤。","authors":"Xiao-Bin Zheng, Chao Wang, Ming Zhang, Bing-Qi Yao, Hai-Yan Wu, Shu-Xian Hou","doi":"10.1007/s11325-024-03216-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Hydrogen sulfide (H<sub>2</sub>S) is a novel gas signaling molecule that has been researched in several physiological and pathological conditions, indicating that strategies targeting H<sub>2</sub>S may provide clinical benefits in diseases such as chronic cardiomyopathy. Here, we reveal the effect of H<sub>2</sub>S on chronic intermittent hypoxia (CIH)-related myocardial damage and its mechanistic relevance to phosphoinositol-3 kinase (PI3K).</p><p><strong>Materials: </strong>Mice were subjected to a 4-week CIH process to induce myocardial damage, which was accompanied by daily administration of NaHS (a H<sub>2</sub>S 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.</p><p><strong>Key findings: </strong>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. H<sub>2</sub>S 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.</p>","PeriodicalId":21862,"journal":{"name":"Sleep and Breathing","volume":"29 1","pages":"43"},"PeriodicalIF":2.1000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exogenous H<sub>2</sub>S targeting PI3K/AKT/mTOR pathway alleviates chronic intermittent hypoxia-induced myocardial damage through inhibiting oxidative stress and enhancing autophagy.\",\"authors\":\"Xiao-Bin Zheng, Chao Wang, Ming Zhang, Bing-Qi Yao, Hai-Yan Wu, Shu-Xian Hou\",\"doi\":\"10.1007/s11325-024-03216-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Hydrogen sulfide (H<sub>2</sub>S) is a novel gas signaling molecule that has been researched in several physiological and pathological conditions, indicating that strategies targeting H<sub>2</sub>S may provide clinical benefits in diseases such as chronic cardiomyopathy. Here, we reveal the effect of H<sub>2</sub>S on chronic intermittent hypoxia (CIH)-related myocardial damage and its mechanistic relevance to phosphoinositol-3 kinase (PI3K).</p><p><strong>Materials: </strong>Mice were subjected to a 4-week CIH process to induce myocardial damage, which was accompanied by daily administration of NaHS (a H<sub>2</sub>S 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.</p><p><strong>Key findings: </strong>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. H<sub>2</sub>S 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.</p>\",\"PeriodicalId\":21862,\"journal\":{\"name\":\"Sleep and Breathing\",\"volume\":\"29 1\",\"pages\":\"43\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-12-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sleep and Breathing\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11325-024-03216-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep and Breathing","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11325-024-03216-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Exogenous H2S targeting PI3K/AKT/mTOR pathway alleviates chronic intermittent hypoxia-induced myocardial damage through inhibiting oxidative stress and enhancing autophagy.
Aims: Hydrogen sulfide (H2S) is a novel gas signaling molecule that has been researched in several physiological and pathological conditions, indicating that strategies targeting H2S may provide clinical benefits in diseases such as chronic cardiomyopathy. Here, we reveal the effect of H2S on chronic intermittent hypoxia (CIH)-related myocardial damage and its mechanistic relevance to phosphoinositol-3 kinase (PI3K).
Materials: Mice were subjected to a 4-week CIH process to induce myocardial damage, which was accompanied by daily administration of NaHS (a H2S 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.
Key findings: 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. H2S 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.
期刊介绍：
The journal Sleep and Breathing aims to reflect the state of the art in the international science and practice of sleep medicine. The journal is based on the recognition that management of sleep disorders requires a multi-disciplinary approach and diverse perspectives. The initial focus of Sleep and Breathing is on timely and original studies that collect, intervene, or otherwise inform all clinicians and scientists in medicine, dentistry and oral surgery, otolaryngology, and epidemiology on the management of the upper airway during sleep.
Furthermore, Sleep and Breathing endeavors to bring readers cutting edge information about all evolving aspects of common sleep disorders or disruptions, such as insomnia and shift work. The journal includes not only patient studies, but also studies that emphasize the principles of physiology and pathophysiology or illustrate potentially novel approaches to diagnosis and treatment. In addition, the journal features articles that describe patient-oriented and cost-benefit health outcomes research. Thus, with peer review by an international Editorial Board and prompt English-language publication, Sleep and Breathing provides rapid dissemination of clinical and clinically related scientific information. But it also does more: it is dedicated to making the most important developments in sleep disordered breathing easily accessible to clinicians who are treating sleep apnea by presenting well-chosen, well-written, and highly organized information that is useful for patient care.
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