首页> 外文期刊>International journal of molecular imaging >Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy
【24h】

Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy

机译:了解荧光显微镜急性实验小鼠肺损伤模型中α-1抗胰蛋白酶的肺沉积

获取原文
获取原文并翻译 | 示例
           

摘要

Human plasma-derived alpha1-antitrypsin (AAT) delivered by intravenous infusion is used as augmentation therapy in patients with emphysema who have a genetic mutation resulting in deficiency of AAT. Inhalation is an alternative route of administration that can potentially increase the efficacy and convenience of treatment. This study was conducted to determine whether delivery to the lungs, initially via the intratracheal (IT) route of administration, would deliver efficacious levels of a recombinant AAT (rAAT) to the site of action in the lungs in mice, ~(125)I-radiolabeled rAAT, fluorophore-conjugated rAAT (rAAT-Alexa488), and NE680 (neutrophil elastase 680, a silent fluorescent substrate of neutrophil elastase which fluoresces in the near-infrared range upon activation by neutrophil elastase) were used to characterize the pharmacokinetics and tissue distribution profile, distribution of rAAT within the lung, and efficacy of rAAT to inhibit neutrophil elastase at the site of action, respectively. The study has demonstrated that rAAT was able to gain access to locations where neutrophil elastase was localized. The histochemical quantification of rAAT activity relative to dose at the site of action provided here will improve confidence in predicting the human dose via the inhalation route.
机译:通过静脉内输注递送的人血浆衍生的α1-抗酸血糖素(AAT)用作具有遗传突变的肺气肿患者的增强治疗,导致AAT的缺乏。吸入是一种替代的给药途径,可能会增加治疗的疗效和便利性。进行该研究以确定是否通过肿瘤内(IT)给药途中的肺部递送,将在小鼠肺中的作用部位提供有效的水平,〜(125)i - 荧光团缀合的拉特(Raat-Alexa488)和Ne680(中性粒细胞弹性蛋白酶680,中性粒细胞弹性蛋白酶键的静音荧光素,含有中性粒细胞弹性蛋白酶激活后的含嗜中性粒细胞弹性蛋白酶的沉默荧光酶)进行表征药代动力学和组织分布型材,肺部内的raat分布,以及Raat在作用部位抑制中性粒细胞弹性蛋白酶的功效。该研究表明,Raat能够进入进入中性粒细胞弹性蛋白酶局部化的位置。本文提供的作用位点的相对于剂量的Raat活性的组织化学定量将提高通过吸入途径预测人剂量的置信度。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号