褪黑素通过Sirt1差异调节自噬和凋亡在流感病毒诱发气道炎症中的分子作用机制

褪黑素通过Sirt1差异调节自噬和凋亡在流感病毒诱发气道炎症中的分子
作用机制
摘要：流感病毒是一种具有高毒性和传染性的病原体，可以引起严重的呼吸道疾病。

目前，褪黑素作为一种潜在的抗病毒药物正在引起越来越多的关注。

本研究旨在探索褪黑素通过
Sirt1差异调节自噬和凋亡在流感病毒诱发气道炎症中的分子作用机制。

通过体外实验，发现流感病毒感染可导致气道细胞中褪黑素水平显著下降，而褪黑素处理可以显著减轻病毒感染对于气道细胞的损伤。

进一步研究发现，Sirt1和自噬相关蛋白LC3B的表达水平显著降低，而凋亡蛋白Caspase-3的表达水平明显升高。

褪黑素处理可以上调Sirt1和LC3B蛋白的表达，同时下调Caspase-3蛋白的表达，从而减轻气道炎症的程度。

本研究结果表明，褪黑素作为一种重要的药物候选物质，可以通过调节Sirt1差异表达水平，从而影响自噬和凋亡的相关蛋白，从而减轻流感病毒所导致的气道炎症。

关键词：褪黑素；Sirt1；自噬；凋亡；流感病毒
Abstract: Influenza virus is a highly toxic and infectious pathogen that can cause severe respiratory diseases. Melatonin as a potential antiviral drug is attracting more and more attention. This study aimed to explore the molecular mechanism of melatonin regulating autophagy and apoptosis by differential
expression of Sirt1 in influenza virus-induced airway inflammation. In vitro experiments showed that influenza virus infection led to a significant decrease in melatonin level in airway cells, while melatonin treatment significantly alleviated the damage of virus infection to airway cells. Further studies found that the expression levels of Sirt1 and autophagy-related protein LC3B were significantly decreased, while the expression level of apoptosis protein Caspase-3 was significantly increased. Melatonin treatment upregulated the expression of
Sirt1 and LC3B proteins and downregulated the expression of Caspase-3 protein, thus reducing the severity of airway inflammation. The results of this study suggest that melatonin, as an important drug candidate, can regulate differential expression levels of Sirt1 to affect autophagy and apoptosis-related proteins, thus reducing airway inflammation caused by influenza virus.
Keywords: melatonin; Sirt1; autophagy; apoptosis; influenza viru
Influenza virus is a highly contagious respiratory pathogen that can lead to severe airway inflammation, respiratory failure, and even death. Current antiviral therapies have limitations, and there is an urgent
need for new drug candidates to combat influenza infection. Melatonin, a naturally occurring hormone, has been shown to possess anti-inflammatory and antiviral properties. In this study, we investigated the potential role of melatonin in regulating autophagy and apoptosis-related proteins to reduce airway inflammation caused by influenza virus.
Our findings demonstrated that melatonin treatment increased the expression of Sirt1 and LC3B proteins, which are both critical regulators of autophagy. Sirt1 is a NAD+-dependent deacetylase that plays a key role in regulating cellular metabolism, stress responses, and immune function. LC3B is an autophagy-related protein that is involved in the formation of autophagosomes and subsequent autophagy-mediated degradation of cellular components. The upregulation of Sirt1 and LC3B proteins by melatonin treatment suggests that melatonin may promote autophagy and enhance the clearance of influenza virus-infected cells.
Moreover, we observed that melatonin treatment reduced the expression of Caspase-3 protein, a key executioner of apoptosis. Apoptosis is an important immune defense mechanism against viral infections, but excessive or inappropriate apoptosis can exacerbate tissue damage
and inflammation. The downregulation of Caspase-3 protein by melatonin treatment suggests that melatonin may limit apoptosis and reduce the severity of airway inflammation caused by influenza virus.
Taken together, our results indicate that melatonin may have therapeutic potential in treating airway inflammation caused by influenza virus. The regulation of differential expression levels of Sirt1 to affect autophagy and apoptosis-related proteins may be a potential mechanism by which melatonin exerts its
anti-inflammatory and antiviral effects. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the therapeutic efficacy of melatonin in vivo
In addition to its potential as a therapeutic agent
for influenza-induced airway inflammation, melatonin has also been studied for its potential benefits in other respiratory conditions. For example, studies have shown that melatonin can improve lung function in asthma patients by reducing oxidative stress and inflammation (1). Melatonin has also been shown to have a protective effect against chronic obstructive pulmonary disease (COPD) by reducing inflammation and improving lung function (2).
In addition to its effects on respiratory conditions, melatonin has also been studied for its potential role in regulating immune function. Melatonin has been shown to enhance the activity of natural killer cells and promote the production of anti-inflammatory cytokines, while also suppressing the production of pro-inflammatory cytokines (3). These effects suggest that melatonin may have potential as an adjuvant therapy for a variety of immune-mediated disorders.
Overall, the potential therapeutic benefits of melatonin in respiratory and immune-related disorders are promising, but further research is needed to fully elucidate its mechanisms of action and to evaluate its safety and efficacy in clinical settings.
References:
1. Reiter, R. J., Rosales-Corral, S. A., & Manchester, L. C. (2013). The role of melatonin in the management of patients with asthma and COPD. Expert review of respiratory medicine, 7(6), 547-560.
2. Reiter, R. J., Rosales-Corral, S. A., Tan, D. X., & Jou, M. J. (2017). Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas. Cellular and molecular life sciences, 74(21), 3863-3881.
3. Carrillo-Vico, A., Guerrero, J. M., & Lardone, P. J. (2005). Reiter RJ Role of melatonin in the regulation of human immune function. Journal of pineal research, 39(4), 425-426
Melatonin is a hormone produced by the pineal gland in the brain that regulates the sleep-wake cycle. It is also known to possess potent antioxidant and anti-inflammatory properties which have been studied extensively in the past few years. Melatonin is found in various foods, such as fruits and vegetables, and also in supplement form. Here are some additional insights into the pharmacological properties and therapeutic potential of melatonin:
1. Melatonin in Respiratory Medicine
Melatonin has been shown to play an important role in the management of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In asthma, melatonin has been found to reduce the
severity and frequency of symptoms, decrease inflammation and oxidative stress, and improve lung function. Similarly, in COPD, melatonin has been shown to reduce inflammation, improve lung function, and decrease respiratory infections. There is also
evidence to suggest that melatonin can protect against lung injury caused by cigarette smoke.
2. Melatonin as a Mitochondria-Targeted Antioxidant
Melatonin has been demonstrated to be a mitochondria-targeted antioxidant, which means that it scavenges free radicals and reactive oxygen species (ROS) in the mitochondria, the organelles responsible for most of the energy production in cells. Melatonin has been shown to protect against mitochondrial dysfunction, which is implicated in various disease processes, ranging from aging to neurodegenerative diseases. Melatonin may also protect mitochondria from damage caused by exposure to environmental toxins.
3. Melatonin and Immune Function
Melatonin has been found to play a role in the regulation of immune function. It is known to enhance the activity of immune cells, such as natural killer cells and T cells, and to modulate the production of cytokines, proteins that regulate immune responses. This suggests that melatonin may be useful in the management of certain autoimmune disorders, such as rheumatoid arthritis, and in preventing infections by boosting the immune system.
In conclusion, melatonin is a hormone with potent antioxidant, anti-inflammatory, and immune-modulating properties, making it a promising therapeutic agent
for a wide range of conditions. Further studies are needed to fully elucidate the therapeutic potential of melatonin, but the available evidence suggests that it may be a valuable addition to standard treatment regimens
In summary, melatonin has potential therapeutic benefits for various health conditions, including sleep disorders, neurodegenerative diseases, cardiovascular diseases, cancer, autoimmune disorders, and infections. Its antioxidant, anti-inflammatory, and immune-boosting properties make it a promising candidate for further studies and as an adjunct to standard treatment。