The protective role of hydrogen sulfide in a mouse model of viral myocarditis induced by Coxsachie-virus B3

Abstract

Objective To investigate the protective role of hydrogen sulfide and the expression of cystathionine gamma-lyase/hydrogen sulfide pathway in a mouse model of myocarditis induced by Coxsachie -virus B3（CVB3）.Methods A total of 110 five-week-old BALB/c male mice were randomly divided into four groups：the control group, viral myocarditis group, sodium bisulfide （NaHS） group （50 μmol/kg） and DL-propargylglycine （PAG） group （40 mg/kg）.The experimental model of viral myocarditis was induced by intraperitoneal injection of CVB 3.Then the four groups were respectively administered with PBS , PBS, NaHS and PAG from day 1 to day 10 after infection.Blood and heart specimens were harvested from 10 mice of each group on day 4 and day 10 for evaluation of myocardial edema .The pathological changes in heart tis-sues were observed through hematoxylin-eosin staining.Levels of H2 S, IL-6 and TNF-αwere measured by ELISA.The expressions of CSE and CVB 3 at mRNA level were determined by quantitative real time PCR （ qRT -PCR ） analysis and the expression of CSE at protein level was detected by Western blot .Results Compared with the control group , the levels of H2 S and the expressions of CSE at mRNA and protein levels were down-regulated in mice with CVB 3-induced myocarditis .With the treatment of NaHS , the levels of H 2 S in serum and tissue were both up-regulated , and the histopathological damage was alleviated .However , PAG as an irreversible CSE inhibitor inhibited the expressions of H 2 S and CSE and aggravated myocardial injury , inflammatory cells infiltration and interstitial edema .Moreover , the RT-PCR analysis also showed that the＆nbsp;expression of CVB3 at mRNA level was inhibited by NaHS but enhanced by PAG .Conclusion The expres-sion of CSE/H2 S pathway is down-regulated in mice with CVB 3-induced viral myocarditis .PAG could pro-mote virus propagation and exacerbate the disease through inhibiting the production of endogenous H 2 S, while NaHS as a H2 S donor has a protective effect on infected myocardium by suppressing virus replication at an early stage . Key words: Viral myocarditis; Coxsachievirus; Cystathionine gamma-lyase; Hydrogen sulfide; Sodium bisulfide; DL-propargylglycine