Biological Activity Test And Primary Pharmacodynamics Study On Fusion Protein Of Recombinant Human Serum Albumin-TPO Mimetic Peptide In Vivo

At present drug side effects from domestic tumor radiation and chemotherapy,hepatitis,HIV/AIDS,Purpura lead to about 10 million of thrombocytopenia patients.Traditional treatments commonly used intravenous immune globulin,a large dose of glucocorticoid,androgen and other immunosuppressive agents,splenectomy,transfusion of platelet concentrates,but the efficacies are mostly unsatisfactory.A kind of natural cytokine of thrombopoietin(TPO)can activate platelet generation by platelet megakaryocyte at any stages,and TPO levels in most thrombocytopenia patients is very low.Therefore,TPO and TPO mimetic peptide(Thrombopoietin mimetic peptide,TMP)became more important drug candidates for the treatment of thrombocytopenia,but seriuos side effects of these drugs and their expense,limit its clinical application.Human serum albumin and TMP fusion protein(rhHSA-TMP)has been obtained in our lab.To detect biological activity in vivo and primary pharmacodynamics of rhHSA-TMP crude and purified samples expressed by CHO and Pichia yeast,normal mice were subcutaneously injected rhHSA-TMP,then platelets were counted under microscope;anti-platelet antiserum(APS)was used to construct the pathologic model of idiopathic thrombocytopenic purpura(ITP)in mice,ITP model mice were treated with rhHSA-TMP subcutaneously,and platelets were counted under microscope;carboplatin was used to induce secondary thrombocytopenia in mice,model mice were subcutaneously injected rhHSA-TMP,platelets were also counted under microscope.The results showed that the level of platelet counts significantly increased after treatment with rhHSA-TMP in normal mice.In addition,rhHSA-TMP can not only significantly increase the level of platelet counts in ITP mice,but also inhibited the decline of platelet counts in secondary thrombocytopenia mice.