ESTABLISHMENT OF NEW IMMUNOSUPPRESSIVE STRATEGY USING GENE TRANSFECTION TECHNIQUE

利用基因转染技术建立新的免疫抑制策略

基本信息

批准号：
10557124
负责人：
FUKUSHIMA Norihide
金额：
$ 5.76万
依托单位：
OSAKA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

It has been reported that endothelial cell activation and apoptosis induced by xenoantibody may play a major role in concordant xenograft rejection as well as direct cell destruction by xenoantibody. Thus, prevention of endothelial cellular apoptosis may prevent graft coronary atheroscrelosis (GCAS). In the present study, the effects of gene transfection of cytoprotective gene, Bcl-2 in graft survival and GCAS was investigated in a hamster-to-rat cardiac transplant (HTx) model in which the recipients were treated with FK506 and cobra venom factor (CVF) to block complement and cellular type rejection.【Material and Method】 14 Golden Hamster hearts were transplanted into Lewis rat abdomen using Ono-Lindsey methods. All rats were given CVF (0.2 mg/Kg ; day 0 and 1) and FK506 (1 mg/Kg from day 0) intramuscularly. These hearts were divided into two groups. In Group-B (+) and -B (-), grafts were transfected by perfusing coronary artery with HVJ-liposome containing vector with Bcl-2 gene and only vector, respectively. Rejection was defined by cessation of palpation from outside. The explanted grafts were evaluated by H-E staining and immunohistochemical staining of Bcl-2.【Results】 Graft survival was not significantly different in these groups. Bcl-2 was expressed only in the graft of Group-B (+) within 3 weeks after HTx. Although GCAS score in Group-B (-) was significantly higher than that in Group-B (+), there was no difference between those more than 4 weeks after HTx.【Conclusion】 Although there was no significant difference in graft survival between both groups, these data suggested that gene transfection of Bcl-2 may prevent endothelial cell activation resulting in preventing graft coronary astheroscrelosis in concordant xenografts.

据报道，内皮细胞的激活和异种抗体诱导的细胞凋亡可能在异种移植物的一致排斥以及异种抗体的直接细胞破坏中发挥重要作用，因此，目前预防内皮细胞细胞凋亡可以预防冠状动脉移植物动脉粥样硬化（GCAS）。研究中，在仓鼠至大鼠心脏移植 (HTx) 模型中研究了细胞保护基因 Bcl-2 的基因转染对移植物存活和 GCAS 的影响，其中【材料与方法】采用Ono-Lindsey法将14只金仓鼠心脏移植到Lewis大鼠腹部。所有大鼠均给予CVF（0.2 mg）。 /Kg；第0天和第1天）和FK506（从第0天开始1mg/Kg）将这些心脏分为两组。 (+)和-B(-)，分别通过用含有Bcl-2基因的载体和仅载体灌注冠状动脉来转染移植物，通过停止外部触诊来评价移植物。 H-E染色和Bcl-2免疫组化染色。【结果】各组移植物存活率无显着差异，仅B组移植物有表达。 (+) HTx 后 3 周内，虽然 B 组 (-) 的 GCAS 评分显着高于 B 组 (+)，但 HTx 后 4 周以上则无差异。【结论】两组之间的移植物存活率没有显着差异，这些数据表明Bcl-2的基因转染可以防止内皮细胞活化，从而预防一致异种移植物中的移植物冠状动脉粥样硬化。