经口腔唾液腺转运的硝酸盐循环对全身健康的重要作用

The important role of the inorganic nitrate cycle mediated by the oral salivary glands in systemic health

稳态是机体健康和疾病的交汇点.保持良好的稳态是健康的必要条件,恢复机体的稳态是扭转疾病状态的关键手段.硝酸盐作为一种天然膳食营养素,广泛存在于日常用水及食物中,是生物体存活不可或缺的物质.在病理状态下,外源性补充的硝酸盐可通过硝酸盐-亚硝酸盐-NO途径,作为内源性NO途径的补充,对机体稳态的维持具有重要意义.与此同时,Sialin和硝酸盐之间相互作用也会参与多种细胞稳态的调节进而对全身稳态作出贡献.目前已证实,外源性补充硝酸盐对机体多系统具有保护作用.硝酸盐是维持机体稳态的重要体系,具有良好的临床应用潜力.本文主要综述了硝酸盐的发现历程及研究现状,并阐明了其在未来应用中可能面临的严峻挑战和应对策略,以期为硝酸盐在机体稳态维持和疾病防治中的应用提供新的研究思路.

Homeostasis represents a dynamic equilibrium process of self-regulation employed by living organisms,which sustains the relative stability of the internal environment of an organism,thus allowing for the continuation of normal physiological functions under ever-changing external conditions.Through homeostatic regulation,organisms adapt to various physiological stimuli and combat pathogenic factors,thereby enhancing their chances of survival.When the delicate balance of homeostasis is disrupted,a cascade of abnormal changes occurs,manifesting as physical symptoms and behavioural abnormalities,commonly recognised as disease symptoms.Homeostatic medicine,rooted in the maintenance of homeostatic balance,includes a systematic investigation into the laws and mechanisms underlying homeostatic regulation at multiple levels,from the molecular and cellular environments to the organ,whole-body,and external environments.This comprehensive approach aims to promote human health,as well as prevent and treat diseases.Inorganic nitrate is widely present in everyday water and food sources and is essential for the survival of organisms.Its historical significance in various aspects of human life,including diet,medicine,and industry,spans over 2000 years in the records of our country.In recent years,extensive research has been conducted to explore the biological activities of nitrate as a natural dietary nutrient.Within the human body,inorganic nitrate undergoes partial reduction to nitrite and nitric oxide due to the action of oral bacteria in saliva.Nitrite is subsequently absorbed into the bloodstream via the intestinal mucosa,where it further reduces to nitric oxide—a process known as the nitrate-nitrite-NO pathway.This pathway plays a pivotal role in regulating bodily nitric oxide levels,and thus,maintaining overall homeostasis.In addition,sialin is a mammalian membrane nitrate transporter,facilitating the transportation of nitrate to salivary glands,where it is secreted into the oral cavity via saliva.The upregulation of sialin expression enhances nitrate influx into cells,establishing a positive nitratesialin feedback loop that protects salivary glands and other organs.Recent studies have revealed the involvement of sialin in various biological functions,further emphasising its significance in homeostatic regulation.Exogenous nitrate supplementation has demonstrated various beneficial effects on the body,including the regulation of vascular tone,antioxidant properties,improvement of muscle performance,gastrointestinal protection,inhibition of inflammatory factor release,modulation of glucose metabolism,and regulation of intestinal flora.The nitrate-sialin system,as a crucial component in maintaining whole-body homeostasis,holds significant promise.As awareness of the advantages of inorganic nitrate for human health deepens,nutritional supplements containing nitrate as the primary ingredient have become increasingly integrated into people’s lives,with their positive effects reported by an increasing number of clinical studies.The effective use and safe management of oral inorganic nitrate represent key challenges in maximising its potential benefits to human health.In this context,this article provides a comprehensive overview of the historical discovery and current research status of inorganic nitrate,elucidating the potential challenges and strategies for future applications.This contribution aims to inspire new research avenues,positioning inorganic nitrate as a promising candidate for health promotion and disease prevention.