| Objective:Glucocorticoid (GC) is the most widely used immunosuppressive drugs in clinical, but it has to bind its receptor to suppress the immune response. In recent years, with improvement of radioligand binding assay of receptor and development of molecular biology, the research of glucocorticoid receptors (GR) has been paid more and more attentions. Studies have shown that the determination of transplant recipients GR has an important role in both clarifying mechanism of immunosuppressive drugs and guiding clinical treatment.Cortisol is endogenous glucocorticoid, and level of serum cortisol is closely related with GR, studying transplant recipients GR and analyzing the change of serum cortisol have an important meaning to understand body glucocorticoids metabolism and to guide rejection treatment.In recent years, with the development of immunosuppressive therapies, the success rate of allogenetic organ transplant obviously improved. Ideal immunosuppressive drugs should be eliminating the rejection of transplant recipients without causing immune deficiency. Immunosuppressive chemicals commonly used in clinical including chemical drug immunosuppressant (such as cyclophosphamide, cyclosporine A, etc.) and inhibitor of immune response effectors. Although these drugs could prolong the survival time of patient in a certain extent, their poison effects are more serious (such as bone marrow inhibition, severe toxicity of liver and kidney, etc.), in the end, patients cannot tolerate and discontinued. On the other hand, these drugs are expensive and economically unbearable. Therefore, the development of new efficiency and low toxicity of immunosuppressive drugs has become a research focus.Astragalus can nourish vitality, different doses of astragalus have different effects on the immune function included immunity enhancement and immunosuppression of double regulation effects. Preliminary study in our laboratory found that Astragalus Membranaceus Injection (AMI) in vivo can significantly prolong the survival time of the allografts. but its definite mechanism, especially about influence on glucocorticoid metabolism is unclear.In this research, we established murine allotransplantation model successfully, studied the change of GR and serum cortisol with radioligand binding assay of receptor and radioimmunoassay, and studied the effect of AMI in vivo on survival of allotransplantation graft after AMI, so as to supply an experimental basis for clinical application AMI against transplant rejection.Methods:1. Establishing murine allotransplantation model;2. Allografts survival condition was observed daily after intraperitoneal injection of Astragalus Membranaceus Injection;3. The amount of GR of recipient's spleen cells at different times after transplantation was measured by Radioligand Binding Assay; and the level of GRmRNA was assayed with RT-PCR;4. The level of serum cortisol at different times after transplantation was measured with Radioimmunoassay.Results:1. The amount of spleen GR and serum Cortisol increased transiently in early stage of transplantation and then decreased, and reach the minimum value at the top period of the rejection (day 14). 2. AMI (60g/kg)or CTX (100mg/kg) administed alone or combined in vivo could prolong the allografts survival time obviously, and the survival quality of the combined administration group obviously better than the group of CTX administration alone.3. AMI alone or combined with CTX could up-regulated the amount of spleen GR, the expression of GRmRNA and level of serum Cortisol at day 14 post transplantation. AMI combined with CTX could make amount of GR increased obviously than CTX alone (P<0.05).Conclusion:1. AMI alone can obviously suppress allotransplantation rejection, and AMI combined with CTX administration in vivo can prolong the allografts survival rate obviously.2. AMI can up-regulate the amount of GR and serum cortisol, and promote the function of endogenous glucocorticoid. |
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