Research On Peptide Immunosuppressor Prevents Liver Transplant Rejection In Rats

Interleukin-2 (IL-2) plays an indispensable role in vivo immune response as an important cytokine. IL-2 exerts its biological effect by the conjugation withInterleukin-2 receptor (IL-2R) expressed on the surface of immunocyte. IL-2R iscomposed of three subunits: α, β and γ . IL-2 initially binds a specific peptide sequence of the IL-2 receptor α and sequentially forms high-affinitycomplex of IL-2/IL-2 receptor α,β, γ .This formation induces cellular signaling and cell proliferation. It has been showed that IL-2 couldn't transduct the stimulate signal to cytoplast if it binds receptor that only consists of β subunit and γ subunit. At the same time, it is found that α chain is not expressed by resting T cells but is expressed by T cells activated, such as abnormal cells in patients with certain leukemias, autoimmune diseases and allograft rejection, so IL-2R α chain inhibitors have been approaches to prolong allograft survival. Allograft rejection is still a major problem in organ transplantation and is one of the most important cause of late graft loss. However, the drugs applied, such as cyclosporin A, exist problem of nonspecificimmunosuppression. The research of immunosuppressive drug is thereby imperative.The first experiment:Objective: To synthesize and evaluate a kind of hexa-peptide that has immunosuppression activity and can specifically conjugatewith IL-2. Method: The hexa-peptide XCSSXX was synthesized, then purified by HPLC and confirmed the molecular weight detected by MS. To observe the influence of the hexa-peptide to the transplantation reject, we constructed the vitro model of the lymphocyte proliferation experiment (LPE) induced by ConA and the lymphocytoblast proliferation experiment induced by IL-2. Result: The molecular weight of hexa-peptide synthesized by MS is 693, it is in coincidence with hexa-peptide. The concentration of the hexa-peptide is 31.25ug/ml. It can significantly suppress the lymphocyte proliferation induced by ConA, the suppress rate is 78.2%. At the same time, it can also significantly suppress the lymphocytoblast proliferation induced by IL-2. Conclusion: The hexa-peptide expresses its immunosuppressive action by suppressing the conjugate of IL-2 and IL-2R.The second experimentObjective: To evaluate the effect of the hexa-peptide to the rat liver transplantation reject and the influence to the Thl and Th2 cytokine. Method: To build the model of rat orthotopic liver transplantation from BN rat to Lewis rat. The rats were divided into four groups: contrast group, SP1 group (peptide 5mg/kg/d), SP2 group (peptide lOmg/kg/d) and SP3 group (peptide 20mg/kg/d). The peptide was injected continuously 7 days after transplantation. To observe the stock time of every group, the histopathological change of liver and the level of cytokine IL-2, IL-4, IL-10 and IFN- y . Result: The stock...