Effect and mechanism of Heme oxygenase-1 alleviating rat liver graft ischemia/reperfusion injury

Objective To explore the effect and mechanism of Heme oxygenase (HO)-1 alleviating rat liver graft ischemia/reperfusion (I/R) injury. Methods Inbred male SD rats were used as donors and recipients. Forty-eight SD rats were randomly divided into control group, suppression group and induced group (donors and recipients of each group were 8,respectively). In control group, no drugs were applied. In suppression group, donors received zinc protoporphyrin (ZnPP) (i. p. ,20 mg/kg), an HO-1 inhibitor 24 h prior to harvest. In induced group, donors received cobalt protoporphyrin (CoPP) (i. p. ,5 mg/kg), an HO-1 inducer 24 h prior to harvest. All livers were harvested and stored with UW solution at 4℃ for 24 h. HO-1 expression in the livers before transplantation was assessed. The rats in all groups were killed at the 6th hour after transplantation, and liver samples were collected, and Kupffer cells were isolated and cultured. Recipients' liver function was tested, and levels of cytokines (TNF-α and IL-6) in the culture supernatant was determined. Histopathological changes of the liver grafts were examined, and the expression of CD14 mRNA and protein in Kupffer cells was detected. Results The HO-1 expression in induced group before liver transplantation was significantly increased. Postoperatively, serum transaminases in induced group were significantly reduced,the histopathological lesions of the liver grafts alleviated,the levels of TNF-α and IL-6 in the culture supernatant of Kupffer cells decreased, and the expression levels of CD14 mRNA and protein in Kupffer cells significantly reduced as compared with the suppression group. Conclusion Induced liver HO-1 up-regulation may inhibit the activation of Kupffer cells,thereby reducing rat liver graft I/R injury. Key words: Heme oxygenase-1;  Kupffer cells;  Ischemia/reperfusion injury;  Liver transplantation