Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats

Abstract

Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than in the CLP + NaHS group (P<0.05). In conclusion, H2S acted as an anti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H2S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H2S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H2S.

Exploring the beneficial role of telmisartan in sepsis-induced myocardial injury through inhibition of high-mobility group box 1 and glycogen synthase kinase-3β/nuclear factor-κB pathway

“…Therefore, an increase in IL-6 and a decrease in IL-10 signifies the onset of inflammation in response to CLP. These results are inconsistent with previous studies [23,24]. Furthermore, there was an increase in the protein expression of HMGB1 in the hearts of CLP-subjected rats.…”

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

“…Multiple studies have confirmed that an appropriate dose of H 2 S has cardiac protective effects (7,9,10), which may be associated with anti-apoptotic, anti-inflammatory and anti-oxidative mechanisms (11). A previous study by the present research team demonstrated that low doses of H 2 S are able to improve the cardiac dysfunction caused by sepsis (12); however, the specific mechanisms involved are not clear.…”

“…Rats (n=56) were randomly divided into 7 groups as follows: Sham group, underwent exposure of the cecum, but not ligation and perforation; sham + NaHS group, received the sham procedure and was administered a 2-ml/kg intraperitoneal administration of 8.9 µmol/kg NaHS 1 h following the surgery; sham + LY294002 group, underwent the sham procedure and was administered a 2-ml/kg intraperitoneal injection of 40 mg/kg LY294002 following the surgery; CLP group, treated with the CLP surgery; CLP + NaHS group, underwent CLP and was administered NaHS (dosage and method as in the sham + NaHS group); CLP + LY294002 group, underwent CLP and was administered LY294002 following the surgery (dosage and method as in the sham + LY294002 group); CLP + NaHS + LY294002 group, underwent CLP and was administered an intraperitoneal injection of NaHS and LY294002 at the aforementioned doses. The doses of LY294002 and NaHS were selected according to previous studies (5,12). Following the procedures, all the rats were free to drink and eat, and 12 h later they were anesthetized again.…”

Inflammasomes: Pandora&rsquo;s box for sepsis

“…In animal model of sepsis, the inhibition of H 2 S or its activation is proven beneficial to the hosts in terms of their survival and reduced tissue/organ injury, including myocardial injury, via improving neutrophil infiltration, K + ATP channel activation, reducing TNF-α, and increasing IL-10 levels 282–284. The CLP-induced sepsis in mice causes a significant increase in the plasma level of H 2 S along with its synthesis in the liver 8 hours post-CLP 282.…”