The Experimental Study Of Inducing Recipient Immune Tolerance To Rat Cardiac Allografts By Using TLR4 Monoclonal Antibodies

Objective This study was designed to investigate the effect of TLR4 monoclonal antibodies (Toll like receptor 4 monoclonal antibodies,TLR4mab)on the recipient immunoloregulation in the model of Wistar to SD rat cardiac allotransplantation. The mechanisms of rejection in allotransplantation will be explored in the model.Materials and methods Donor(Wistar rat) and recipient(SD rat) were divided randomly into two groups. Group A(no treatment): The heart from Wistar rat was transplanted into the abdomen of SD rat without any pre-treatment; Group B(TLR4mAb Group ): The recipients SD rats were injected with TLR4mab 100ug/kg in abdomen and recieved TLR4mAb injection every 48 hours intraperitoneally at the same time afte transplantation. The grafted heart mean survival time (MST),the expression of TNF-α,IFN-γ,IL-2,IL-10,TGF-β1 in blood and the expression of NF-κB in donor heart were observed.Results (1)MST:Group A: 5.6±0.89d; Group B: 25.2±3.40d; The MST of Group B was prolonged significantly, P<0.05.(2) The results of TNF-αin the peripheral blood of recipient's(pg/ml): Group A TNF-αof the first postoperative day,the third postoperative day and the fifth postoperative day were 112.90±21.23,213.75±21.85,469.53±47.35, Group B TNF-αof the first postoperative day,the third postoperative day and the fifth postoperative day were 27.73±6.82,37.04±5.97,96.08±13.59; Group B is much lower significantly than Group A,P<0.05. (3)The results of IFN-γin the peripheral blood of recipient's(pg/ml): Group A IFN-γof the first postoperative day,the third postoperative day and the fifth postoperative day were 147.01±13.80,340.58±13.62,516.21±40.34, Group B IFN-γof the first postoperative day,the third postoperative day and the fifth postoperative day were 62.78±10.14,97.85±17.52,144.40±28.91; Group B is much lower significantly than Group A,P<0.05.(4) The results of IL-2 in the peripheral blood of recipient's(pg/ml): Group A IL-2 of the first postoperative day,the third postoperative day and the fifth postoperative day were 1.96±0.03,2.78±0.02,4.84±0.03,Group B IL-2 of the first postoperative day,the third postoperative day and the fifth postoperative day were 1.12±0.03,1.55±0.04,1.84±0.04; Group B is much lower significantly than Group A,P<0.05.(5) The results of IL-10 in the peripheral blood of recipient's(pg/ml): Group A IL-10 of the first postoperative day,the third postoperative day and the fifth postoperative day were 49.17±3.70,51.40±3.79,46.09±2.54,Group B IL-10 of the first postoperative day,the third postoperative day and the fifth postoperative day were 26.01±1.40,27.53±2.02,26.42±1.15; Group B is much lower significantly than Group A,P<0.05.(6) The results of TGF-β1 in the peripheral blood of recipient's:Group A and Group B were not significantly different between the before and after sugery.(7) NF-κB(western-blot): Group A: 172.50±9.55, Group A:73.61±6.31; Group B is much lower significantly than Group A,P<0.05.Conclusions (1)Using TLR4mab can affect the TLR4-MD2-LPS path way to lower Th1/ Th2 path way,lower the related factors such as IL-2, IL-10, IFN-γto prolong the survival time of allograft. (2)Using TLR4mab can affect the level of NF-κB down, affecting TNF-α, TGF-β1 and other factors to reduce acute rejection and to prolong the survival time of allograft. (3) We can observe to use TLR4mab can significantly reduce the acute vascular rejection (AVR) occurs, but can not completely overcome its occurrence.