Abstract
When histiocyte are ischemic for a certain time and blood supply is suddenly restored, the pathological condition of rapidly aggravated tissue damage is called ischemia reperfusion injury, which is mainly caused by a large amount of Ca2+ influx and oxygen free radicals attacking ischemic histiocyte. Ischemia reperfusion injury can increase the incidence rate and mortality of some diseases, such as acute myocardial infarction, ischemic stroke, acute renal injury, intestinal obstruction, hyperkalemia and multiple organ failure, and it also brings great challenges to surgery such as organ transplantation. However, the current treatment methods for ischemia-reperfusion are still very limited. Fortunately, increasing evidence suggests that reasonable concentrations of hydrogen sulfide may play a powerful organ protective role in ischemia-reperfusion injury, mainly through mechanisms such as anti apoptotic, antioxidant, stress reduction, regulation of autophagy, and inhibition of inflammation. Therefore, hydrogen sulfide has profound clinical conversion prospects in the treatment of I/R injury. This article systematically summarizes the generation and physiological effects of endogenous hydrogen sulfide, as well as its protective mechanisms in different systems such as the heart, brain, kidney, liver, retina, and testes. In addition, the clinical transformation prospects and current challenges of hydrogen sulfide in ischemia-reperfusion injury were discussed.
Key words: hydrogen sulfide,ischemia-reperfusion injury,antioxidant,Inhibition of apoptosis,Inhibition of inflammation
Introduction:
Over the years, hydrogen sulfide (H2S) has been known for its rotten egg like odor, toxicity and environmental hazard. The toxicological mechanism of H2S is mainly to inhibit the cytochrome c oxidase in mitochondria, thus causing chemical asphyxia of cells[1, 2]. Cytochrome c oxidase (COX) is an important electron transmitter in the respiratory chain, which participates in the process of cellular respiration. Its activity is inhibited, which reduces the utilization of oxygen in mitochondria, leading to cell hypoxia[3, 4]. In recent years, human understanding of H2S has gradually shifted from toxic substances to gas transmitters with therapeutic drug potential. In 1989, hydrogen sulfide was proven to exist in the human brain and may play a certain physiological role[5]. In 1996, Japanese scientists demonstrated that hydrogen sulfide is a potential signaling molecule that can be produced by Cystathionine-β-synthase (CBS) and involved in neurotransmission[6]. The following year, they discovered that Cystathionine-γ-lyase (CSE) is another enzyme that produces[7]. Subsequently, Wang et al. confirmed that hydrogen sulfide is the third physiological signaling molecule, except for carbon monoxide (CO) and nitric oxide (NO)[8]. Since then, the field of sulfide research has developed rapidly and the research results have become richer,In a 2005 paper, Blackstone et al. reported in a pioneering manner that H2S can induce a reversible pseudo-death-like state in mice. They hypothesized that H2S-mediated induction of pseudo-death may have beneficial medical applications, such as ischemia-reperfusion (I/R) injury or organ preservation after trauma[9].
Ischemia reperfusion injury (IRI) is a special pathological phenomenon characterized by the sudden aggravation of tissue damage, or even irreversible damage, after a certain period of tissue ischemia restores blood supply[10, 11]. As the name suggests, I/R injury can be divided into two stages. Ischemic stage refers to the restriction of blood supply to tissues or organs, which is generally caused by embolus blocking arteries, causing imbalanced tissue metabolism, leading to severe tissue hypoxia and microvascular dysfunction. The subsequent tissue reperfusion stage will further enhance the activation of programmed cell death, congenital and adaptive immunity[12-14]. The tissue damage caused by IRI will greatly increase the incidence rate and mortality of some diseases, such as acute myocardial infarction, ischemic stroke, acute renal injury, intestinal obstruction, hyperkalemia and multiple organ failure, and also bring great challenges to surgical operations such as artery bypass grafting, limb replantation and organ transplantation[15, 16]. At present, there is still some controversy over the exact molecular mechanism related to the occurrence of IRI, and treatment strategies are also hindered. However, the gas mediated cellular signaling pathway may provide a new direction for its therapeutic strategy. Previous studies have found that NO and CO2 have a protective effect on ischemia-reperfusion injury, and the role of hydrogen sulfide cannot be underestimated.
In this review, we will discuss the understanding of the protective mechanisms of H2S in different organs, especially the multifunctional advantages of this gas in vivo and its clinical potential in ischemia-reperfusion injury.