Abstract:

Objective  To investigate the expression and significance of monocyte chemotactic protein-1(MCP-1) in cardiac transplantation rejection as well as the role of nuclear factor of kappa B (NF-κB) pathway. Methods  Heterotopic cervical heart transplantation was performed on SD rats with Wistar rats as doners by using cuff-technique. The SD rats were randomly divided into 4 groups, with 12 in each group. Rats in the acute rejection group received no treatment. Rats in the CsA group were treated with 10mg/kg cyclosporine A after transplantation, and cardiac allografts were harvested 60 to 90 days after transplantation. Rats in the immunological tolerance group were pretreated with donor splenocyte (SPC) and cyclophosphamide (CP), and then heterotopic cervical heart transplantation was performed 14 days later. Rats in the PDTC group were treated with Pyrrolidine dithiocarbamate (PDTC) 100mg/kg every day for 15 days. The allograft myocardial fibrosis was then observed with Masson stain and the expression of MCP-1 was detected with immunohistochemistry and Western blotting. Results  The survival time of the cardiac allograft in acute rejection group, CsA group, immunological tolerance group and PDTC group was (6.53±2.48)d, (93.51±20.07)d, (201.42±40.36)d and (142.37±24.64)d respectively. The survival time of PDTC group was significantly longer than that of acute rejection group and CsA group (P<0.05), and the degree of myocardial fibrosis in PDTC group was much lower. The expression of MCP-1(IOD) of cardiac allograft in acute rejection group, CsA group, immunological tolerance group and PDTC group was (1.86±0.23), (1.58±0.16), (0.57±0.15) and (1.16±0.28) respectively. The IOD in immunological tolerance group was markedly lower than in the other three groups (P<0.05), and that in PDTC group was obviously lower than in acute rejection group and CsA group (P<0.05). Conclusion  The expression level of MCP-1 is positively correlated with the severity of graft rejection. As a result, the detection of MCP-1 can indicate the state of allograft. PDTC, as the inhibitor of NF-κB, can significantly relieve the rejection of cardiac allograft by inhibiting the expression of MCP-1.

Key words: Graft rejection; Nuclear factor of kappa B; Monocyte chemotactic protein-1; Pyrrolidine dithiocarbamate