Role of nitric oxide in xenotransplant cardiac rejection

一氧化氮在异种移植心脏排斥反应中的作用

• 批准号: 6338421
• 负责人: ROBERT S FARIVAR
• 金额: $ 4.2万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6338421
• 关键词: baboons; chemical structure function; colorimetry; enzyme induction /repression; enzyme inhibitors; gene expression; genetically modified animals; heart transplantation; heart valve transplantation; immunocytochemistry; immunosuppressive; nitric oxide; nitric oxide synthase; northern blottings; serum; swine; transplant rejection; transplantation immunology; urinalysis; western blottings; xenotransplantation

DESCRIPTION (Verbatim from the applicant?s abstract) Transplantation is now a standard treatment for end stage heart failure. With the persistent lack of donors, however, xenotranplantation may be a future option. The previous barrier of hyperacute rejection associated with xenotransplantation has been gradually overcome with the combination of transgenic pigs expressing human complement regulatory proteins and new immunosuppressive regimens. To date, no one has systematically studied the activation status of nitric oxide (NO) in any xenotransplantation model. We propose to examine the role of NO in the phenomenon of delayed xenograft rejection. Specifically, in the pig-to-baboon cardiac transplantation model, we will be examining expression of NOS 2 (inducible NO synthase) via Northern and Western blotting, immunohistochemistry and by measuring the stable end-products of NO in serum and in urine. NO donors and NO synthase inhibitors will be administered to xenotransplanted animals and the transplanted heart will be examined. With a better understanding of the activation status of NO synthase, it is hoped to uncover potential novel therapies for transplant rejection.

描述（逐字化申请人的摘要）现在是一个移植 终阶段心力衰竭的标准治疗。持续缺乏 但是，捐助者的异种倾向可能是未来的选择。上一个 与异种移植相关的超急性排斥的障碍已经 通过表达人的转基因猪的组合逐渐克服 补体调节蛋白和新的免疫抑制方案。迄今为止，没有 一个人已经系统地研究了一氧化氮（NO）的激活状态 任何异种移植模型。我们建议检查NO在 延迟异种移植排斥的现象。具体而言，在猪到baboon中 心脏移植模型，我们将检查NOS 2的表达 （可诱导的无合酶）通过北部和蛋白质印迹，免疫组织化学 并通过测量NO在血清和尿液中的稳定最终产物。没有捐助者 并且不会对异种移植动物和 将检查移植的心脏。有了更好的理解 非合酶的激活状态，希望能发现潜在的新颖 移植排斥的疗法。