Protective effects of heme oxygenase-1 on delayed xenograft rejection

Objective To investigate the effect of heme oxygenase-1(HO-1) on immunity response in delayed xenoheart transplantation and its mechanism. Methods The cobalt protoporphyrin (CoPP) was used to induce HO-1 in the model of NIH-Wistar cervical cardiac transplant, combined with immunosuppressor cyclosporine A (CSA) and cyclophosphamide (CYP), respectively. The survival time was evaluated; the HO-1, IL-1β, INF-γ, TNF-α, and STAT-3 were detected by immunohistochemstery and Western blotting. The macrophage was stained by CD68 antibody and the differences among various intervene factors were compared. Results The survival time of transplanted heart in group of CoPP was longer than that of control group (t = 2.693 6, P 0.05); the survival time of transplanted heart in groups of CoPP plus CSA and CoPP plus CYP were longer than that of CSA and CYP, respectively (t = 2.851 1, P 0.05); the survival time of transplanted heart in group of CoPP plus CSA plus CYP was the longest (t = 3.864 4, P 0.001). The expressions of TNF-α and IL-1β, except INF-γ, in CoPP group were lower than those in control group (t = 2.636 4, P 0.05); the expressions of the three cytokines in CoPP combined CSA and CYP group were lower than that in other group. The STAT-3 in CoPP group was not significant difference compared with CSA and CYP (t = 1.085 4, P 0.05), but higher than that in control group (t = 10.125 4, P 0.001), and lower than that in CoPP combined CSA or CYP (t = 2.816 4, P 0.05). The expression of STAT-3 in CoPP combined CSA and CYP group was the highest compared with the other groups (t = 2.560 5, P 0.05). The number of CD68 cell in control group was more than that in CoPP group (t = 3.183 7, P 0.01), and which in CoPP combined CSA and CYP group was the least compared with the other groups (t = 2.509 9, P 0.05). Conclusion HO-1 combined CSA and CYP can up-regulate STAT-3 and down-regulate CD68 infiltration in cardiac xenograft and decrease expression of preinflammation cytokine IL-1β, TNF-α, and IFN-γ, thus postpone the delayed xenograft cardiac rejection.