| Objective and Background: Cardiac transplantation is a widely accepted therapy for the treatment of end-stage congestive heart failure, but the rejection occurred after transplantation has restricted the effect of therapy. Since the immunosuppressant was used to inhibit the allograft rejection in 1983, the One-year survival rate has already been increased to 80%, but it also brings some fatal complications such as tumor and infection. So it's a valuable avenue for conquering the rejection to go on doing research on the mechanism of allograft rejection and to find new method or medicament to inhibit the rejection or induce the immunological tolerance. Traditional immunology recognizes that the adaptive immune response induced by T cells is the main mechanism for the allograft rejection, and the Complement has not direct effect on the allograft rejection. But in 1996, Julian R Pratt used sCR1 to inhibit C3 in serum of the kidney allotransplantation model in Lewis rat to DA rat. He found that the grade â…¢ acyte rejection was deferred from 5 days to 9days, and the extent of infiltration by T cells of both CD4+ and CD8+ phenotype were obviously reduced. In 2002, Julian R Pratt found that most C3-negative mouse donor kidney (C57BL/6H-2b) transplanted into C3-positive mice (B10.BrH-2k) survived for at least 100 days, whereas control grafts from C3-positive donors were rejected within 14 days. The author suggested that local production of C3 excreted by PTECs had a significant effect on T-cell stimulation. The literature above indicate that the Complement does participate in the process of allograft rejection as certain mode, and farther investigation has crucial value not only for extending the mechanism of allograft rejection, but also for exploring new method and medicament to inhibit the allograft rejection.Up to now, there is not any investigation about the role of Complement in the mechanism of allograft rejection induced by Cardiac allotransplantation. In order to investigate this topic initiatively, we plan to use CVF to deplete C3 in serum of the Cardiac allotransplantation model in Wistar rat to SD rat, whereafter we observe the survival time and the changes of pathology of allograft at different time.Methods: To achieve our goals, we conducted the following works: 1. We modified the technique that was described by Ono to establish an abdominal heterotopic cardiac allotransplantation model in Wistar rat to SD rat.2. In order to test the anticomplementary activity and the side-effect of this kind of CVF, we injected low dose CVF in the SD rat and used the CH50 test to measure the variation of C activity in serum.3. We divided the animal models into two groups (control group and CVF group). First, we observed the survival time of allograft. Second, we killed five rats chosen respectively from the two groups at day 1,3,5,6,7, and compared the pathology grade for acute rejection, the Complement activity in serum, the deposition of C3 on tissue, the extent of infiltration by T cells of both CD4+ and CD8+ phenotype.Results: (1) We had succeeded to establish the abdominal heterotopic rat cardiac allograft model. (2) Complement activity was inhibited to less then 10% of pretreatment (normal) activity at days 1 to 3 after injection CVF. At day 10, hemolytic activity was still depressed to a mean of 62.02%. (3) The survival time of cardiac allograft treated with CVF was significantly prolonged, even some of the allograft survived beyond 60 days. In control animals, with uninhibited C activity, C3 was deposited in the cardiac vascular from days 1 to 7, and their endothelial characterized swelling, lifting, and stripping. The grafts of CVF-treated animals, in contrast, showed no C3 staining, and their endothelial had not obvious change. Compare with the control animals, the extent of infiltration by T cells of both CD4+ and CD8+ phenotype were significantly reduced in CVF-treated animals.Conclusions:1. The modified Ono technique is a stable method to establish the animal model of heterotopic cardiac allotr...
|
PDF Full Text Request