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Lung Transplantation Using Primates Aiming Its Clinical Application.

灵长类动物肺移植的临床应用。

基本信息

批准号：
62480291
负责人：
FUJIMURA Shigefumi
金额：
$ 4.29万
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 (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

In our previous examinations of rat lung transplantation,investigation of bronchoalveolar lavage fluid (BALF) was indicated as a good diagnostic probe for rejection monitoring. In order to assure the usefulness of this method in clinical application, the investigation of BALF in primate lung transplants was conducted. Left lung allotransplantation were performed in Japanese monkeys (Macaca fuscata). From these experiments, following results were obtained.l.Inhalation anesthesia by enflurane with pancronium bromide was preferable for Japanese monkey.2.In transplantation procedures, more gentle manipulations were necessary rather than in dogs.3.Immunosuppression was given by cyclosporine (20mg/kg/day,intramuscular injection) and azathioprine (2.0mg/kg/day,subcutaneous injection).To acquire enough immunosuppression, administration of cyclosporine was necessary start one week before the transplantation.4.The bronchoalveolar lavage was done by intrabronchial injection and aspiration of 10ml PBS with 3mm diameter bronchofiberscope wedged basal banch of bronchus.5.The changes of BALF associated with a progression of rejection were summarized as follows: 1)the number of total cells were increased; 2)lymphocytes and neutrophils were increased in number; and 3)T lymphocyte subset ratio (CD4/CD8) was decreased. The results were consistent with histological studies of specimens taken by open lung biopsies.From these results, it was shown that the primate lung transplantation model was established technically. BALF was proved to be a good diagnostic probe for rejection monitoring in primate.

在我们以往的大鼠肺移植实验中，支气管肺泡灌洗液（BALF）的检测被认为是监测排斥反应的一种很好的诊断手段。为了进一步证实该方法的临床应用价值，我们对灵长类动物肺移植后BALF进行了研究。在日本猕猴（Macaca fuscata）中进行了左肺同种异体移植。结果表明：1.日本猴采用安氟醚吸入麻醉和潘可溴铵吸入麻醉效果较好; 2.在移植过程中，操作要比犬轻; 3.免疫抑制剂采用环孢素（20 mg/kg/天，肌肉注射）和硫唑嘌呤（2.0mg/kg/天，皮下注射）。为了获得足够的免疫抑制，术前1周开始给予环孢素A。4.支气管肺泡灌洗，5. BALF中细胞总数增加，淋巴细胞和中性粒细胞增多，T淋巴细胞亚群比例（CD_4/CD_8）降低。结果与开放性肺活检标本的组织学研究一致，表明灵长类动物肺移植模型在技术上是建立的。事实证明，支气管肺泡灌洗液是灵长类动物排斥反应监测的良好诊断探针。