Protective effects of N-acetylcysteine regulating HIF-1a / iNOS signal pathway on ischemic-reperfusion injury in rat heart transplantation

Objective To observe the effect of HIF-1a/iNOS signaling pathway on myocardial ischemia-reperfusion injury in rat heart transplantation and the protective mechanism of N- acetylcysteine (NAC) on donor heart after cardiac transplantation in rats. Methods Eighty healthy male Lewis rats were randomly divided into 3 groups, the control group (0.3 ml saline was infused via inferior vena cava 30 min before donor harvest or implantation), NAC donor pretreatment group [NAC (30 mg/kg.w) was injected into the vena cava of donor rat 30 min defore donor harvest], and the NAC receptor pretreatment group(NAC 300 mg/kg.w was injected into the vena cava of the recipient rats 30 min before transplantation.The 30 min was injected into the vena cava of the recipient rats). A transplant model was established and the graft was obtained after 24 h transplantation.The expression of iNOS, HIF-1a and mRNA in cardiac muscle tissue was detected by immunohistochemistry and Real time-PCR. Results HIF-1a protein expression in graft myocardial tissue was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group (P<0.05), the differences were statistically significant (2.72±0.17 vs.2.24±0.23 vs.3.14.±0.16, F=56.26, P=0.000). The iNOS protein expression in NAC donor pretreatment group, and NAC recipient pretreatment group were lower than that in the control group(1.52±0.18 vs.1.61±0.19 vs.3.30±0.18, F=232.345, P=0.000), the differences were statistically significant(P<0.05).24 h after transplantation, the differences in graft myocardial tissue HIF-1a and iNOS mRNA among the three groups were statistically significant (F=7.467, 16.490, P=0.003, 0.000). The expression of iNOS mRNA in the NAC receptor pretreatment group was significantly lower than that in the control group (P<0.05). Conclusion HIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation, and the protective effect of NAC on donor heart maybe mediated via this pathway. Key words: N-acetylcysteine; Heart transplautation; Ischemia-reperfusion injury(IRI); Hypoxia inducible factor 1a(HIF-1a); Inducible nitric oxide synthase (iNOS)