| Aim: As the most effective therapy for end-stage heart disease , heart transplantation has been used in many hospitals. But the graft rejection, especially the acute rejection, is still an obstacle for thoracocardiac doctors. How to control the graft rejection is the key to heart transplantation. Graft rejection is essentially an immounological reaction and the intraction between lymphocyte and lymphocyte lymphocyte and capillary endothelial cell is an important component in it. And this intraction is mediated by a series of cytokines and adhesion molecules. Data of research show that the excessive expression of Interleukin- 1 beta (IL-l |3 ) and Intercelullar Adhesion Molecule-1 (ICAM-1) after heart transplantation play an important role in the infiltration of lymphocytes and the cardiac tissue injury during the acute graft rejection. Catherine pointed outthat over expression of IL-1 and ICAM-1 were bounded up with triggering Nuclear Factor-KB (NF-KB) and forming a positive feedback loop after heart transplantation. Actived NF-KB can also up-regulate the expression of other inflammatory mediators genes , such as indicuble nitric oxide synthase and phospholipaseA2 and so on. Progressive exacerbation of pathogenesis in acute rejection may be associated with these mediators via inflammatory cascade reaction. Sulfasalazine(SSA) is the specific and potent inhibitor of NF-KB , which can suppress the activation of NF-KB and reduce the expression of many inflammatory mediators by inhibit the phosphorylation of inhibitor-KB(I-KB). No reports about NF-KB inhibitor used in acute rejection of heart transplantation have been found. To investigate the protective effect of SSA on transplanted rat heart , we established improved Ono's rat heart transplant model and used SSA to treat acute rejection, the expression of IL-1 |3 and ICAM-1 in transplantated myocardium tissue and the injury of the transplantated heart were quantitatively measured.Methods: Adult healthy clean inbred strain closed colony rat are chosen, the range of their weight was 250-3 OOg. A rat heterotopic cardiac transplant model with SD donors and Wistar recipients was used. Group A: control group of Wistar to Wistar rat heart transplantation; Group B: SD to Wistar rat heart tarnsplantation;Group C: SD to Wistar heart translantation and treated with SSA. In each group the transplanted hearts were harvested on day 3 day5 and day7 respectively. The grafts received immunohistochemical and histopathological examinations to examine the expression of ICAM-1 and acute rejection. Radioimmunoassay and multimedia pathology imaging analysis system were used for quantitative measurment of IL-1 P and ICAM-1 experssion.Results: 1. IL-1 0 content: Faint IL-1 experssion and there were no statistical differences at different time points in group A(P<0.01). In group B, IL-1 content significantly elevated on day3, and came to the peak on day5 to day, and there were significant statistical differences compared with group A(P<0.01). In group C after treatment of SSA, IL-1 content significantly decreased, there were statistical differences compared with group B(P<0.01); there were also statistical differences compared with group A(P<0.05).2. ICAM-1 content: In group A, faint expression were found and there were no statistical differences at different time points(P>0.05). But in group B, ICAM-1 elevated expression on capillary endothelial cell of grafts on day3, and it came to peak on day 5, there were significantly statistical differences compared with group A(P<0.01). After treatment with SSA in group C, the contentof ICAM-1 significant decreased compared with group B, and there were statistical differences (P<0.01), though it was still higher than that of group A.3. Histopathological change of transplanted heart: In control group the cardiac tissue were nearly normal, only rare infiltration of lymphocytes were found. In group B there were a few of lymphocytes infiltrated in and the cardiac tissue were normal too on day3, but on day5 there were mu... |
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