Bonkohara Y, Hachida M, Nonoyama M, Hoshi H, Imamaki M, Saito S, Koyanagi H
Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College.
Nihon Kyobu Geka Gakkai Zasshi. 1994 Jan;42(1):61-8.
15-Deoxyspergualin (DSG) attracts a lot of attention as an immunosuppressive drug which has less side effects these days. In the present study, we researched the rescue effect of DSG for acute rejection on heart transplantation (HTX) by using rat models. We performed 40 heterotopic heart transplantation models. We injected them DSG (group A: 5 mg/kg/day, group B: 10 mg/kg/day) intravenously through 3 days, starting from the 3rd day the 4th day, and the 5th day after HTX. Our previous study showed the pathology on the 3rd day after HTX corresponded to mild rejection, the 4th day to moderate rejection, and the 5th day to severe rejection. One day after the injection was completed, the recipients were sacrificed. The rescue effect was histopathologically assessed by H-E stain, and the action mechanism of DSG was considered by immunohistochemical stain using monoclonal antibodies, which were against CD4 positive cells, CD8 positive cells, and macrophages. In result, the rescue effect of DSG was significant in all groups, in comparison with controls, which had no immunosuppression. And the rescue effect of group B was superior to group A. We also found using a immunohistochemical technique, that DSG inhibited the accumulation of CD4 and CD8 positive cells. We concluded the rescue effect of DSG for acute rejection on HTX was significant, especially in 10 mg/kg/day even in the severe rejection. And the suppression of helper and cytotoxic T cells accumulation might be one of the action mechanisms of DSG.
15-去氧精胍菌素（DSG）作为一种副作用较小的免疫抑制药物，近年来备受关注。在本研究中，我们使用大鼠模型研究了DSG对心脏移植（HTX）急性排斥反应的挽救作用。我们建立了40个异位心脏移植模型。从心脏移植后的第3天、第4天和第5天开始，连续3天通过静脉注射给予DSG（A组：5mg/kg/天，B组：10mg/kg/天）。我们之前的研究表明，心脏移植后第3天的病理表现对应轻度排斥反应，第4天对应中度排斥反应，第5天对应重度排斥反应。注射完成后1天，处死受体。通过苏木精-伊红（H-E）染色对挽救效果进行组织病理学评估，并使用针对CD4阳性细胞、CD8阳性细胞和巨噬细胞的单克隆抗体通过免疫组织化学染色来探讨DSG的作用机制。结果显示，与未进行免疫抑制的对照组相比，DSG在所有组中均具有显著的挽救效果。并且B组的挽救效果优于A组。我们还通过免疫组织化学技术发现，DSG抑制了CD4和CD8阳性细胞的积聚。我们得出结论，DSG对心脏移植急性排斥反应具有显著的挽救作用，尤其是在剂量为10mg/kg/天的情况下，即使在重度排斥反应中也是如此。并且抑制辅助性和细胞毒性T细胞的积聚可能是DSG的作用机制之一。
