| Background Cardiac allograft transplantation is the final effective means of treating the end-stage heart disease, but so far the long-term survival of patients with cardiac allograft is not satisfactory. Studies have shown that the survival rates of heart transplant recipients were84.5%,78.2%and72.5%respectively, when1,3and5years after heart transplantation. Cardiac allograft vasculopathy (CAV) and myocardial fibrosis are the main causes of disfunction of the transplanted heart. So to find a method to effectively suppress chronic rejection of heart transplantation is the direction of the current study. Chemokines as the key factor of transplant rejection can recruit specifically antigen presenting cells (APC) and T lymphocytes into the tissue of transplanted organs, so as to stimulate and promote the progress of inflammation, resulting in the impairment of graft function and even loss of organ function, so chemokine is a kind of important medium in the prosess of transplant rejection. Monocyte chemotactic protein-1belongs to CC chemokine subfamily members, it is an important factor leading to inflammatory cells infiltration and fibrosis in the transplanted organs by recruiting T lymphocytes and macrophages. Nuclear factor of kappa B may have the role to regulate the expression of a variety of factors including cytokines and chemokines, some studies have shown that, NF-κB pathway may play a central role in the regulation of transplant rejection.Objective To investigate the expression and significance of monocyte chemotactic protein-1(MCP-1) in cardiac transplant rejection as well as the role of nuclear factor of kappa B (NF-κB) pathway, by inhibiting specifically NF-κB pathway with pyrrolidine dithiocarbamate (PDTC) and detecting the expression of MCP-1in the transplanted heart. 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 into4groups, with12in each group. Rats in the acute rejection group received no treatment. Rats in the CsA group were treated with10mg/kg cyclosporine A after transplantation, and cardiac allografts were harvested60to90days after transplantation. Rats in the immunological tolerance group were pretreated with donor splenocyte (SPC) and cyclophosphamide (CP), and then heterotopic cervical heart transplantation was performed14days later. Rats in the PDTC group were treated with Pyrrolidine dithiocarbamate (PDTC)100mg/kg every day for15days. The allograft myocardial fibrosis was then observed with Masson stain and the expression of MCP-1was 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). The Percentage of fibrosis of the cardiac allograft in acute rejection group, CsA group, immunological tolerance group and PDTC group was (25.37±9.45)%,(81.74±8.53)%,(43.19±6.36)%and (63.50±6.94)%respectively, and the degree of myocardial fibrosis in PDTC group was much lower than CsA group (P<0.05). 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).Conclusions The expression level of MCP-1is positively correlated with the severity of graft rejection. As a result, the detection of MCP-1can 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. |
PDF Full Text Request