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Research of Glucosida Tripterygii Combined with Cyclosporine A in Heart Transplantation Rats

Author: ZuoZhiGuo
Tutor: YangShaoJun
School: Kunming Medical College
Course: Surgery
Keywords: Cyclosporin A Tripterygium glycosides Rat heart transplant Immunosuppressive
CLC: R654.2
Type: Master's thesis
Year: 2009
Downloads: 103
Quote: 0
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Abstract

Background: December 4, 1967, Cape Town, South Africa, Barnard, MD, for the first time successfully completed human allogeneic heart transplants, to make the whole world to whom panic and excitement. After many years of basic research and clinical trials, allogeneic heart transplantation is the only effective means of treatment of end-stage heart pump failure and non-correction of congenital heart disease. With the progress of the development of modern medical technology and immunosuppressive drugs, heart transplantation, an increasing number of end-stage pump failure patients benefit, to the high-quality or even a normal life, a heart transplant has been more definitely. The immune response to the foreign body reaction in the human body to foreign, it is for diseases caused by bacteria, viruses and other is a very effective defensive role. Unfortunately, the human body does not distinguish between all recognize it as non-own thing, even if it is to save lives and transplantation to the heart, kidneys and other organs will be excluded mercilessly, so that makes the organ transplant case of to great difficulties. Higher success rate to make organ transplants, in addition to continuously improve surgical techniques and improved variety of medical devices, such as the use of cardiopulmonary bypass the heart-lung machine, the most important thing is you want to find the root of immune rejection and organ transplant immune exclusion method. At present, the donor heart preservation, surgical techniques, postoperative infection is no longer the most important factors that hinder the success of heart transplantation. Maintenance of heart function after transplantation requires lifelong immunosuppressive drugs to prevent or control a variety of rejection. Currently, the most commonly used cyclosporin A, azathioprine (AZA), prednisone (SABC), etc., are designed to non-specifically blocking T-cell activation, that is, the graft rejection of the original mechanism of the reaction. But unfortunately, these drugs exist toxic side effects, the narrow therapeutic window, and other issues. With the growing number of long-term survival of patients, these issues have become increasingly prominent, including liver and kidney toxicity, dyslipidemia, diabetes, and increased risk of infection and malignancy risk. All of which led to a 1-year survival rate after surgery is not yet more than 90%, only less than 50% 10-year survival rate after surgery Obviously, the further development of the heart transplant need to be more innovative, safer, more effective immunosuppressive The agent used in organ transplantation. In recent years, a new immunosuppressive agents have been developed, including IL-2 receptor monoclonal antibody (Daclizumab, daclizumab), FK506 (tacrolimus) - can block T cell activation depends on interleukin-2 and Ray Pa neomycin (sirolimus) - can block the regulation of the cell cycle. Early clinical trials have proved that these new drugs can improve the short-term effect of organ transplant rejection, however, long-term use of these drugs have a considerable number of toxic side effects. So choose new drugs or anti-rejection method will continue to be an important direction of the Medical Research. Objective: After years of experimental research and clinical trials, has found a variety of traditional Chinese medicine has immunosuppressive effects, but also not a substitute for the clinical use of anti-rejection drugs. Applications due to the current anti-rejection drugs have considerable side effects, people began to explore Chinese medicine combined with clinical immunosuppressants to prevent immune rejection of the transplant recipients. The purpose of this test is as cyclosporine A (half the normal dose) combined with Tripterygium glycosides (Glucosida Tripterygii T Ⅱ) after anti-rejection drugs, by observing the rat heterotopic transplant the heart beat of time and pulsatile strength and The body serum a concentration of interleukin-2 to determine the effect of anti-rejection. Experiments on Chinese medicine combined with cyclosporine A immunosuppressant based on research data, and the mechanism of action of Chinese anti-transplant rejection, and how to make the traditional Chinese medicine in the treatment of transplantation immune rejection further Application. Donor: male SD rats, Wistar rats as recipient abdominal aorta end to side anastomosis of the ascending aorta of the donor heart and receptor excision of the left kidney of the receptor, the donor heart pulmonary artery receptors in the left renal vein homemade polyethylene tube inserted directly into law connected. Formation recipient abdominal aorta → donor aortic → coronary → myocardial → the coronary venous → right atrium → right ventricle → pulmonary receptors the blood circulation of the inferior vena cava of the left renal vein → → open vascular clips, and recovery for the hard work for. The postoperative daily touch abdomen observation transplant heart throb situation, the transplanted heart beat the landmark transplant success for more than 24 h. Divided into 3 groups: control group (intraperitoneal injection of saline per day), cyclosporine A (CsA group) (5mg/kg/d intraperitoneal injection) the CsA T Ⅱ group (CsA2.5mg/kg, according to the different treatment of postoperative / The d T II 25mg/kg/d intraperitoneal injection). Group 3 receptor after transplantation intraperitoneally injected with drugs to transplant heart arrest. Observed the strength of the transplanted heart beating and beating time, four days after blood collection, centrifuged to obtain serum, a constant temperature of -20 ℃ to to frozen spare, the levels of serum IL-2 was measured by ELISA. Results: the the transplant heart throb strength in the CsA group and CsA T Ⅱ group difference was not statistically significant, but were significantly better than the control group. Days CsA group and CsA T Ⅱ group transplanted heart survival was significantly longer than that of the control group, and no significant difference between the two. CsA group with CsA TII group and the control group serum IL-2 levels were significantly decreased the, of CsA TII group lower than the CsA group difference was statistically significant between the two. Conclusions: 1. Tripterygium glycosides with anti-allograft rejection. Tripterygium glycosides Joint application of cyclosporine A half dose of cyclosporine A transplanted heart, no difference in survival time compared with cyclosporine A alone. Cyclosporine A can reduce the amount of cyclosporine A in combination with Tripterygium glycosides, and also reduce the content of serum IL-2.

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