Research Of Glucosida Tripterygii Combined With Cyclosporine A In Heart Transplantation Rats

Background:In 1967 Dr.Barnar carried on the 1st human heart transplantation in situ successfully at Cape Town South Africa and the whole world was terrified and excited.After many years of basic researches and clinical trials,the current that the allogeneic heart transplantation is the treatment of end-stage heart "pump failure" and the correction of congenital heart disease can not be the only effective means.With the development of modern medical technology and the progress of immunization in the research,the heart transplants the last stage pump failure patient who finally benefit from high-quality and even to live a normal life,the heart transplants obtains the affirmation more and more.The immune response is the human body to the external foreign matter response, because it regarding the bacterium,the virus and so on vigorous sickness which causes is one kind of very effective defense function.Unfortunately,the body will not be different from all others by its non-recognition of objects,even if it is to save lives and transplantation of the heart,kidneys and other organs will be ruthlessly excluded, so that makes an organ transplant case that is extremely difficult.To obtain a higher transplant success rate,in addition to continuously improve the surgical technique and improvement of various medical devices,such as the use of cardiopulmonary bypass the heart-lung machine,the most important thing is to find the root causes of immune rejection of organ transplants and resolving immune exclusion method.At present,the donor heart preservation,surgical techniques, postoperative infection is no longer impede the success of a heart transplant the main factor.However,cardiac function after transplantation to maintain the need for lifelong use of immunosuppressive drugs to prevent or control rejection.At present,the most commonly used cyclosporine A,azathioprine,prednisone, are designed to block non-specific activation of T cells and graft rejection is the original mechanism.Unfortunately,these drugs there are side effects,and a narrow therapeutic window and so on.And long-term survival of patients with increasing number of these issues have become increasingly prominent,including the liver and kidney toxicity,dyslipidemia,diabetes and increased risk of infection and the occurrence of malignant tumors and so on.All of which resulted in the survival rate after 1 year has not been more than 90%,after a 10-year survival rate below 50% only.It is clear that the further development of heart transplantation on the need for a more innovative,safer,more effective to the immunosuppressive agents used in organ transplantation.In recent years,new immunosuppressive agents continue to come out, including IL-2 receptor monoclonal antibody(Daclizumab,Zenapax,FK506 (tacrolimus)-to block dependent on IL-2 activation of T cells and Rapamycin (sirolimus)-can block the cell cycle regulation of a number of points.Early clinical trials have proven that these drugs can improve the organ transplantation with short-term effects of exclusion.However,the long-term use of these drugs have a considerable number of toxic side effects.So choose a new anti-rejection drugs or methods,will continue to be an important direction of medical research.Objective:After many experiments and clinical trials,people found some traditional Chinese drugs had immunosuppressive ability,but now it could not replace chemical immunosuppressant in clinic.At present there is no drug satisfied because of toxicity and side effects.Many people have tried to use traditional Chinese drugs and immunosuppressant together to prevent and treat graft rejection.This experiment evaluates the synergicanti-rejection effect of Glucosida Tripterygii(Tâ…¡)combined with cyclosporine A(CsA)with half normal dose via heterotopia rat cardiac allograft by observing the transplanted hearts'beating time and theconcentration of interleukin-2 in recipient serum.And this test provided the basic data about different dose during the research of the anti-rejectionability of traditional Chinese drugs combined with immunosuppressants CsA.Draw off some view on traditional Chinese drug's anti-rejection mechanism,and how to use traditional Chinese drugs on anti-rejection broadly and advancedly.Methods:Male SD rats served as donors and Wistar as recipients,the ascending aorta of allograft was anastomosed to the recipient abdominal aorta,The recipient underwent a left nephrectomy,and The pulmonary of donor heart connects with the receptor left renal vein by homemade's polyethylene pipe directly.Form the blood route:receptor abdominal aorta-donor arteriae aorta-aeteria coronaria-cardiac muscle-vena coronaria-right atrium-right ventricle-arteria pulmonalis-receptor left renal Vein-inferior vena cava.After heart transplantation,touching abdomen daily to observe the transplanted heart.That transplants surviving more than 24 hours marks success.Post operation,the mice were randomly divided into three even groups:control group(NS abdomen injection),Group CsA(5mg/kg/d abdomen injection),Group CsA+Tâ…¡(CsA2.5mg/kg/d+Tâ…¡mg/kg/d abdomen injection),and Observing transplanted heart beating intensity and beating time.The 4th day after blood collection,offcenterl serum,-20oC temperature cryopreservation standby. Measured by ELISA serum levels of IL-2.Results:There is no statistic difference in transplanted hearts'beating intensity between Group CsA and Group CsA+Tâ…¡,and the heart beating intensity of these two Groups are stronger than control group.And the transplanted hearts'beating time of these two groups are longer than control group,with no statistic difference.The concentration of interleukin-2 in serum is obviously lower than control group,and the concentration of Group CsA+Tâ…¡is lower than concentration of Group CsA,this difference has statistic significance.Conclusions:1.Glucosida Tripterygii(Tâ…¡)has immunosuppression effect and can be used as anti-rejection drug to protect grafts;2.We reduced half dose of Cyclosporine A,the transplanted heart survival time was not decreased when combined with Glucosida Tripterygii(Tâ…¡);3.Dose of Cyclosporine A can be reduced when combined with Glucosida Tripterygii(Tâ…¡)and can reduce the serum content of IL-2.