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Changes in myocardial beta-adrenergic receptors during acute rejection of heterotopically transplanted rat hearts

异位移植大鼠心脏急性排斥反应过程中心肌β-肾上腺素能受体的变化

基本信息

批准号：
03670650
负责人：
OHMI Mikio
金额：
$ 1.41万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

This study was designed to establish a new reliable method of detecting acute rejection in transplanted heart by evaluation of changes in myocardial beta-adrenergic receptors.First, we conducted an experiment to analyze the density (B-max) of the myocardial beta-adrenergic receptors in heterotopically transplanted rat isografts(n=6) and allografts(n=6). Hearts from Fisher donors were transplanted either to the Fisher rats (isografts) or Lewis rats (allografts). Histological examinations of the allografts showed mild to moderate rejection on the 7th and 14th day and showed severe rejection on the 21st day after transplantation. The B-max values in the allografts and isografts similarly increased significantly above the normal level on the 7th and 14th day after transplantation. The B-max in allografts on the 21st day decreased significantly below the normal level while that in isografts remained at the normal level.We therefore conducted the second experiment to evaluate the difference between the changes in B-max values of both iso- and allografts in the earlier (3rd-5th day) phase. We observe the B-max value decreased significantly below normal level in the allografts which showed no histlogical rejection yet, whereas the B-max value in the isografts did not change.These study opened up the possibilities of establishment of new methods of an early detection of acute rejection before development of histological rejection in transplanted cardiac grafts. Because the loading status of transplanted hearts may affect the myocardial B-max values, we are trying to establish a heterotopi cally transplanted working rat heart model, which would be valuable in evaluating early change in loaded myocardial beta-adrenergic receptors during acute rejection.

为了建立一种通过心肌β-肾上腺素能受体的变化来检测移植心脏急性排斥反应的新方法，本研究首先对大鼠同种和同种异位移植心脏的β-肾上腺素能受体密度（B-max）进行了分析。将来自Fisher供体的心脏移植到Fisher大鼠（同种移植物）或刘易斯大鼠（同种移植物）。术后第7、14天移植物组织学检查为轻度至中度排斥反应，第21天为重度排斥反应。移植后第7天和第14天，同种异体和同系移植物的B-max值均显著高于正常水平。同种异体移植后第21天B-max明显低于正常值，而同系移植后仍维持正常值，因此我们进行了第二个实验，以评价同系移植和同种异体移植早期（第3 ~ 5天）B-max值变化的差异。我们观察到在未发生组织学排斥反应的同种异体心脏移植物中，B-max值明显低于正常水平，而在同种异体心脏移植物中，B-max值无明显变化，这些研究为建立在移植心脏发生组织学排斥反应之前早期发现急性排斥反应的新方法提供了可能。由于移植心脏的负荷状态可能影响心肌的B-max值，因此我们试图建立一种异位移植的大鼠工作心脏模型，该模型对评价急性排斥反应时负荷心肌β-肾上腺素能受体的早期变化具有重要价值。