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Effect of Combined Drugs Pretreatment and Transforming Growth Factor Beta 1 Gene Transfer on Guinea Pig to Rat Discordant Cardiac Xenograft

Simplified Cervical cardiac xenotransplantation model of guinea pigs-SD rat were successfully established by modifed Heron's technique by cuff vessel anastomosis. A appropriate dosage of purified Chinese cobra venom factor administration showed excellent effects to exhaust complement C3 in rats recipients, can prevent discordant cardiac xenografts from hyperacute rejection and establish the acute xenograft vascular rejection mode. Combination of cyclosporin A, leflunomide and extract of gingko biloba with various mechanisms and effector cells, pretreatment on acute xenograft vascular rejection can significantly prolong discordant xenograft survival time, which were associated with increase expression of graft protective gene, attenuation myocardial cell apoptosis and alleviation pathological lesion of acute xenograft vascular rejection. Intracoronary infusion recombinant adenovirus vector mediated immunosuppressive cytokines transforming growth factor betal gene transfer to guinea pig donor hearts during cold preservation after harvest, the methods was efficient and effectively. Extensive expression of exogenous gene attenuated inflammatory cell infiltration in the xenografts, relieved impairment of immune reaction and significantly prolonged xenograft survival time. Gene transfer can induce localized expression of therapeutic suppressive cytokines within donor xenografts that would make this new approach applied in the field of immunosuppressive therapy.

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