Animal and Therapeutics Core

项目总结（见说明）： 动物和治疗学核心（核心B）的总体目标是为动物研究提供集中和标准化的程序，以检测项目1-4中拟定的治疗药物的疗效。 Core将提供两种最常用的鼠肺纤维化模型：（1）博来霉素诱导的肺纤维化模型;和（2）AdTGF- B1[223/225]诱导的肺纤维化模型。Core还将为4个项目的3种不同候选药物提供3种不同途径的标准化药物递送服务：（1）项目3、4的ncRNA（miR和siRNA）的气道/非手术气管内递送;（2）全身/口服 施用（管饲）口服有效的小分子Src激酶抑制剂AZD 0530用于项目2;（3）胸膜内递送ncRNA和小分子Src激酶抑制剂用于项目1。核心负责人刘瑞明博士和几位项目负责人在这些动物模型和 所提出的用于药物递送的技术。 为了向所有项目提供标准化服务，核心将：1）协调实验动物的采购、卫生服务和护理; 2）提供后勤和技术支持，确保实验方案正确实施; 3）制备并确定表达腺病毒的滴度。 组成型活性TGF-β 1（AdTGF-β 1 [223/225]）; 4）所有项目均进行鼻内（AdTGF-β 1 [223/225]）和胸腔内（博莱霉素）滴注，以诱导肺纤维化; 5）每日或隔日通过灌胃、非手术胸腔内滴注和胸腔内滴注给予治疗药物， 6）在实验期间监测和记录动物的异常反应，必要时对动物实施安乐死。将这些动物模型和治疗程序集中在核心B中将有助于每个项目的主要研究者的工作，并确保每个项目的实验将使用相同的标准化动物处理方法进行。因此，这些服务的集中化将允许使用更少的动物总数（具有成本效益），并允许比较不同药物和同一药物不同给药途径之间的结果。

PROJECT SUMMARY (See instructions): The overall goal of the Animal and Therapeutics Core (Core B) is to provide centralized and standardized procedures for the animal studies to test the efficacy of therapeutic agents proposed in each of Projects 1-4. The Core will provide two of the most commonly used murine lung fibrosis models: (1) Bleomycin-induced pulmonary fibrosis model; and (2) AdTGF- B1[223/225]-induced lung fibrosis model. The Core will also provide standardized drug delivery service through 3 different routes for 3 different candidate drugs for 4 Projects: (1) airway/non-surgical intratracheal delivery of ncRNAs (miRs and siRNAs) for Projects 3, 4; (2) systemic/oral administration (gavage) of an orally effective small molecule Src kinase inhibitor AZD0530 for Project 2; (3) intra-pleural delivery of ncRNAs and the small molecule Src kinase inhibitor for Project 1. The Core leader Dr. Rui-Ming Liu and several Project leaders have extensive experience with these animal models and with the techniques used for the drug delivery proposed. To provide the standardized service to all the projects, the Core will 1) Coordinate purchase, health services, and care for experimental animals; 2) Provide logistical and technical support in ensuring that experimental regimens are implemented correctly; 3) Prepare and determine the titers of the adenovirus that expresses constitutively active TGF-B1 (AdTGF- B1[223/225] ); 4) Conduct intranasal (for AdTGF- B1[223/225] and intratracheal (for bleomycin) instillation to induce lung fibrosis for all Projects; 5) Administrate the therapeutic drugs through gavage, non-surgical intratracheal instillation, and intrapleural instillation daily or every other day as designed in each Project; 6) Monitor and record abnormal responses in animals during experimental periods and euthanize animal if necessary. Centralization of these animal models and treatment procedures in the Core B will facilitate the work of the Principle Investigators of each Project and ensure that experiments with each Project will be performed using identical and standardized methods for animal handling. Centralization of these services therefore will allow for fewer total numbers of animals to be utilized (cost-effective) and for the comparison ofthe results between different drugs and different administration routes ofthe same drug.