Abstract
Objective To examine whether the increase of carbon monoxide (CO) induced by oral methylene chloride (MC) administration in recipients before heart transplantation would protect heart grafts against isehemia/reperfusion (I/R) injury associated with transplantation and to explore the possible mechanism.Methods Inbred male Balb/c mice were used as donors and recipients to establish cervical heart transplantation model Recipients were treated with either MC (100 mg/kg or 500 mg/kg,per os)(group MC 100 mg,n=10;group MC 500 mg,n=12) or olive oil(0.15 ml,per os.group olive,n=10) 3 h prior to anesthesia.Age-matched norwlal mice served as controls (group N,n=5).The serum COHb and the CO content of myocardial tissue were measured at 0,1,3,6,12,24 h after oral MC administration.Half of recipients were killed at 3 and 24h after transplantation for senum or cardiac graft samples.The serum cTnI levels,the mRNA levels of TNF-α,IL-10,Bcl-2,Bax.the protein levels of NF-κB and the ultrastructures of myocardium were examined.Results As tompared with group olive.the serum COHb and tissue CO were increased significantly and peaked within 3 h in group MC 100 mg and group MC 500 mg.The serum cTnI levels in group MC 100 mg and group MC 500 mg were significantly decreased (P 0. 05) in the heart grafts. As compared with group N, the myocardial NF-κB activation was increased significantly in group olive,group MC 100 mg and group MC 500 mg (P 0. 05). The myocardial ultrastructure was also alleviated significantly in group MC 100 mg and group MC 500 mg as compared with group N. Conclusion The increase of CO induced by MC in recipients suppresses pro-inflammatory and pro-apoptotic gene expression and efficiently ameliorates transplant-induced heart I/R injury. The possible mechanism does not seem to be associated with down-regulation of the NF-κB signaling pathway. Key words: Carbon monoxide; Nuclear factor kappa B; Inflammation; Apoptosis; Ischemia/reperfusion injury; Heart transplantation
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