The Effect Of Minidose CsA Combined With CVF In Preventing Rat Cardiac Allograft Acute Rejection

Objective and Background: Heart transplantation is the only way to solve the heart failure of terminal stage. With the development of surgical intervention and transplantation theory, It have gain great success in clinic. But the immune rejection after transplantation restrict the effect of operation. The basic problem threaten the graft is the chronic disfunction. although it have prolonged the one-year and five-year survival rate of allograft by using the Immunosuppressant durg. But the Immunosuppressant durg have the shortage of side effect and huge cost, as well as it can not suppess the immune rejection completely. So It is very important to find a cheaper and safer strategy.The traditional theory of transplantation immunity believe the major mechanism of allograft hyperacute rejection is T cell mediated specific immune response to aim directly at alloantigen, such as major histocompability complex(MHC). Recently, the accumulative data showed the complement system also partake the process of the allograft hyperacute rejection, but it is not very clear. It not only have great meaning in allograft hyperacute rejection theory to elucidate the mechanism, but also could lay a foundation for invention of new Immunosuppressant method and durg.Methods: To achieve our goals, we conducted the following works:1. Use modified Ono's method, employed the Wistar to SD rat cardiac allograft model.2. The animal model divide into five groups by blank control, full-dose CsA, half-dose CsA, CVF and minidose CsA combined with CVF treatment, respectively. Then detect the seruim complement activity, observe the survival time of the allograft, In the day of, the rats were sacrificed and analyse the pathological rejection grade by HE, the CD4~+,CD8~+T cells infiltration by immunohistochemistry.3. Detect IL-2, IL-10 mRNA expression of donor heart by RT-PCR.Results:1. The Wistar to SD rat abdominal heterpotopic cardiac allograft model established successful:2,The activity of complement can be effectively inhibited by injecting mini-dose CVF periodic;3,Compared with the blank group, the graft survival time of the other groups was prolonged significantly(P＜0.01), Compared with group treated by the full-dose CsA, half-dose CsA or CVF, the graft survival time of group treated by the minidose CsA combined with CVF was also prolonged significantly(P＜0.01); 4,Compared with the blank group, the pathological rejection grade also reduced and CD4~+, CD8~+ T cells infiltration become mild in the other groups, expecially in the group of full-dose CSA and minidose CsA combined with CVF treatment; 5,The significant difference of IL-2 and IL-10 mRNA expression was not found between the group of the blank control and CVF treatment, or between the group of half-dose CSA and minidose CsA combined with CVF treatment.Conclusions: The result suggested the CVF and the CSA has cooperativity in preventing rat cardiac allograft hyperacute rejection, when apply minidose CSA combined with CVF, the rejection effect would be redued significantly, even compared with the full-dose CSA treatment. CVF could inhibit the T cells infiltration by applied sololy orcombined with CSA, But it could not regulate the secretion of inflammatory cytokines such as IL-2 or IL-10. The mechanism of its anti- rejection effect still be hazy and need progressive study.1. The Wistar to SD rat cardiac allograft model using the modified Ono technique is a stable and ideal method to establish the animal model of heterotopic cardiac allotransplantation.2. CVF combined with minidose CsA can effectively inhibit the acute rejection of rat heart transplantation, the graft survival time of the combined group was prolonged significantly compared with the group treated by CsA only;3.In the combined group, the pathological rejection grade was reduced and lessened, CD4~+ T, CD8~+ T cells infiltration become mild. CVF has no inhibitory action on the expression of IL-2,IL-10 through the RT-PCR method. We can conclude CVF's strengthening the activity of inhibitory rejection of CsA is not through regulating the secretion of inflammatory cytokines such as IL-2.