权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Interleukin-10 Gene Transfer to The Airway of Rat Lungs for Prevention of Lung Allograft Rejection

将白细胞介素 10 基因转移至大鼠肺气道以预防肺同种异体移植排斥

基本信息

批准号：
14370401
负责人：
OKADA Yoshinori
金额：
$ 8.58万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370401/
关键词：
lung transplanation allograft rejection tolerance gene transfer IL-10 遺云子導入

项目摘要

Background : The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). We examined the feasibility of transferring the vIL-10 gene into rat lungs by intra-bronchial instillation and the subsequent effects of delivered vIL-10 on acute lung AR. Methods : First, the adenoviral β-galactosidase vector (adv-β-gal) particles were instilled into the rat lung and protein synthesis of β-gal was confirmed by histochemical staining. Next, the ability of the adenoviral vIL-10 vector (adv-vIL-10) transfection to modify AR was examined in a highly histoincompatible rat lung transplant model (BN→Lew). Donor left lungs were transfected with 3x10^8 pfu/0.3mL of adv-vIL-10 or adv-β-gal 3 days before transplantation. On day 6 post-transplant, AR was graded histologically (stage 0-4). Several pathological categories of inflammation were also scored on a scale of 0-4. Results : The stage of AR was 3.75±0.5 in the adv-vIL-10 group and 4.0±0 in the adv-β-gal group, and the difference did not reach a statistically significant difference. There were no significant differences either in the degree of edema (3.5±0.6 vs. 4±0), vasculitis (1.5±0.6 vs. 1.5±0.6), necrosis (1.5±0.5 vs. 1.75±1.3), and hemorrhage (2.3±1.0 vs. 2.5±0.6). Conclusion : This preliminary study showed that transfection of adv-vIL-10 did not seem to reduce lung AR significantly, as opposed to the results of our previous experiments in a rat cardiac allograft model. This discrepancy might be explained by the immunogenecity of the adenoviral vector, and the ability of liposome mediated IL-10 delivery to reduce lung AR is currently under investigation.

背景：表达具有潜在免疫调节能力的基因的能力可以减少同种异体移植排斥反应（AR）。我们研究了通过支气管内滴注将vIL-10基因转移到大鼠肺中的可行性以及递送的vIL-10对急性肺AR的后续影响。研究方法：首先，将腺病毒β-半乳糖苷酶载体（adv-β-gal）颗粒滴注到大鼠肺中，并通过组织化学染色证实β-gal的蛋白合成。接下来，在高度组织不相容的大鼠肺移植模型（BN→Lew）中检查腺病毒vIL-10载体（adv-vIL-10）转染修饰AR的能力。移植前3天，供体左肺用3 × 10^8 pfu/0.3mL的adv-vIL-10或adv-β-gal转染。在移植后第6天，对AR进行组织学分级（0-4期）。炎症的几种病理学类别也以0-4的量表评分。结果如下：AR分期Adv-vIL-10组为3.75±0.5，Adv-β-gal组为4.0±0，差异无统计学意义。水肿（3.5±0.6 vs. 4±0）、血管炎（1.5 ± 0.6 vs. 1.5 ± 0.6）、坏死（1.5±0.5 vs. 1.75±1.3）和出血（2.3±1.0 vs. 2.5±0.6）的程度均无显著差异。结论：该初步研究表明，与我们先前在大鼠心脏同种异体移植模型中的实验结果相反，转染adv-vIL-10似乎并没有显著降低肺AR。这种差异可能由腺病毒载体的免疫原性解释，脂质体介导的IL-10递送减少肺AR的能力目前正在研究中。