[The impact of hydrogen sulfide on the heme oxygenase-1/carbon monoxide system in Coxsackie virus B3-induced myocarditis in mice].

Objective To explore the impact of hydrogen sulfide (H2S) on the heme oxygenase-1/carbon monoxide pathway in Coxsackie virus B3 (CVB3)-induced murine myocarditis (VMC) model. Method A total of 70 inbred male Balb/c mouse (4-6 weeks old) were randomized into the following four groups: Normal, VMC, PAG and NaHS (n=10 for Normal, n=20 for VMC, PAG and NaHS groups). Mice in Normal group were non-infected mice treated with intraperitoneal injection of sterile phosphate-buffered saline daily for 10 days.Mice in VMC group received intraperitoneal CVB3 injection (0.1 ml 10-5.69TCID50m·ml-1·d-1 and PBS for 10 days), and mice in PAG group received additional intraperitoneal DL-proparglygylcine injection (40 mg·kg-1·d-1 for 10 days), mice in NaHS group received additional intraperitoneal NaHS injection (50 μmol·kg-1·d-1 for 10 days). All mice were sacrificed on day 10th, and body weight and heart weight, the ratio of heart weight to body weight were compared among groups.Pathological changes of heart tissues were observed microscopically by HE and the histopathologic scores were valued.The content of COHb was tested after the gathering of blood specimens while reverse transcription-polymerase chain reaction was used to detect myocardial HO-1 mRNA expression. Results (1) Pathological findings in myocardium: hearts sections in Normal group were normal and no inflammatory cells and necrosis were found.A notable cellular infiltration, interstitial edema, vascular hyperemia and necrosis were observed in heart section of VMC, PAG and NaHS group.Extensive inflammations and larger area of myocardial cells necrosis were evidenced in PAG group and above changes were significantly reduced in NaHS group.(2) Comparison of the ratio of heart weight to body weight and histological scores of myocardium: the ratio was significantly higher in the VMC, PAG, NaHS groups than in Normal group (P<0.05), which was higher in PAG group and lower in NaHS group as compared with VMC group (both P<0.05). The histopathologic scores of all CVB3 innoculation groups were higher than in the Normal group, which was higher in PAG group and lower in NaHS group as compared to VMC group (both P<0.05). (3) The content of blood COHb in VMC, PAG or NaHS group was significantly higher than that in Normal group (P<0.05), which was significantly lower in PAG group, and higher in NaHS group as compared to VMC group (both P<0.05). (4) The mRNA expression of myocardial HO-1 detected by RT-PCR: weak expression was observed in Normal group, which was significantly upregulated in VMC, PAG and NaHS groups (P<0.05), which was downregulated in PAG group and upregulated in NaHS group as compared to VMC group (both P<0.05). (5) Correlation analysis: blood COHb concentration was positively correlated with myocardial HO-1 mRNA expression(r=0.927, P=0.000), negatively correlated with histopathologic scores(r=-0.753, P=0.000)and the histopathologic scores were negatively correlated with the myocardial HO-1 mRNA expression (r=-0.754, P=0.000). Conclusions H2S could play a protective role in murine CVB3 myocarditis model through inducing HO-1 expression and upregulating HO-1/CO pathway. Key words: Myocarditis; Hydrogen sulfide; Carboxyhemoglobin; Heme oxygenase-1; Carbon monoxide