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.