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FK506, Denudation of Donor Endothelial Cells and Bafilomycin A_1, a Selective Inhibitor of Vacuolar H^+-ATPase, Inhibit Neointimal Hyperplasia in Rat Cryopreserved Aortic Allograft

FK506，供体内皮细胞的剥脱和巴弗洛霉素 A_1（液泡 H+-ATP 酶的选择性抑制剂）抑制大鼠冷冻保存的同种异体主动脉移植物中的新内膜增生

基本信息

批准号：
14571289
负责人：
OSAKO Motohiko
金额：
$ 2.11万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571289/
关键词：
graft prosthesis allograft neointimal hyperplasia endothelial cell cryopreservation durability

项目摘要

Cryopreserved allografts have been utilized as alternatives for autografts. However, quality of allografts has been compromised by neointimal hyperplasia (NH). Although allo-immune response and cryopreservation procedures have been implicated in the mechanism of cryopreserved allograftpathy, the exact nature of this pathophysiology remains unknown. We have, therefore, investigated the possible involvement of allo-immune response and V-ATPase in NH in rat cryopreserved aortic allografts.Cryopreserved thoracic aorta from donor rats were implanted to the infra-renal abdominal aorta of recipient rats. The grafts removed 14 days after surgery were evaluated for all-immune response by counting the number of lymphocytes with positive immunostainung for CD8^+(×10^4/mm^2), and for NH by calculating the area ratio of intima to media.Allo-immune response in untreated allografts and allografts treated with Bafilomycin A_1 (BA_1) were significantly higher than untreated isografts, allografts treated with FK506 and allografts of which endothelial cell (ETs) were denuded (p<0.05). Untreated isografts and allografts of which ETs were denuded before transplantation and treated with FK506 and with BA_1 showed significant inhibition of NH compared to untreated allografts (p<0.05). Neointimal cells showed positive immunostaining for vimentin, but negative for HF-35 and CGA-7, indicating that these cells were dedifferentiated SMCs.FK506, denudation of donor ETs and BA_1 inhibit NH early after transplantation of rat cryopreserved aortic allografts. The mechanism of inhibition of NH induced by inhibition of allo-immune response may involve immunosuppression whereas that exerted by BA_1 may be mediated through direct growth suppression of dedifferentiated SMCs via inhibition of V-ATPase.

冷冻保存的同种异体移植物已被用作自体移植物的替代品。然而，同种异体移植物的质量已受到新生内膜增生（NH）的影响。虽然同种免疫反应和冷冻保存程序已被牵连在冷冻保存同种异体移植病的机制，这种病理生理学的确切性质仍然未知。因此，我们研究了同种异体免疫反应和V-ATPase在大鼠深低温保存的同种异体主动脉移植物NH中的可能参与。通过计数CD 8 ^+免疫染色阳性的淋巴细胞数量，评估术后14天取出的移植物的全免疫应答结果表明，未处理的同种异体移植物和BA_1处理的同种异体移植物的免疫反应均显著高于未处理的同种异体移植物，FK 506处理的同种异体移植物和内皮细胞剥脱的同种异体移植物（p<0.05）。与未处理的同种异体移植物相比，FK 506和BA_1处理的同种异体移植物和移植前剥脱血管的同种异体移植物对NH的抑制作用显著（p<0.05）。FK 506、供体血管剥脱和BA_1均能抑制大鼠同种异体主动脉移植后早期NH的发生。BA_1抑制NH的机制可能是通过抑制V-ATP酶而直接抑制去分化SMC的生长。