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Gene therapy for severe bacterial pneumonia and sepsis.

严重细菌性肺炎和败血症的基因治疗。

基本信息

批准号：
16390456
负责人：
YAMADA Yoshitsugu
金额：
$ 6.02万
依托单位：
The University of Tokyo (2006)Yokohama City University (2004-2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

On the basis of recent studies dealing with acute lung injury, keratinocyte growth factor (KGF) has been shown to have certain protective effects against various injurious stimuli and to promote epithelial repair. Thus, in this study, we examined whether transient overexpression of KGF in the lung by the intratracheal administration of KGF-expressing adenovirus vector attenuates hyperoxia-induced acute lung injury in mice. The present data show that the adenovirus-mediated transfer of KGF cDNA successfully expressed high level of KGF in airway epithelial cells, and consequently raised significant lung epithelial cell proliferation, improved oxygenation, and decreased mortality. Furthermore, there was minimal vector-associated inflammation. We suggest that KGF gene transduction into lungs is a promising potential treatment for acute lung injury and would be a useful tool for regeneration research.

最近对急性肺损伤的研究表明，角质形成细胞生长因子(KGF)对各种损伤刺激具有一定的保护作用，并能促进上皮修复。因此，在这项研究中，我们研究了通过气管内注射表达KGF的腺病毒载体在肺内瞬时过表达KGF是否减轻了高氧诱导的小鼠急性肺损伤。目前的研究结果表明，腺病毒介导的KGF基因转移成功地在呼吸道上皮细胞中表达了高水平的KGF，从而显著促进了肺上皮细胞的增殖，改善了氧合，降低了死亡率。此外，与病媒相关的炎症也很少。我们认为，肺内转导KGF基因是治疗急性肺损伤的一种有前景的治疗方法，并将成为再生研究的有用工具。