Mechanisms of Vascular Injury in the preterm lung

早产儿肺血管损伤的机制

• 批准号: 6607215
• 负责人: SUHAS KALLAPUR
• 金额: $ 12.5万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607215
• 关键词: angiogenesis; bronchopulmonary dysplasia; cardiovascular injury; chemokine; cytokine receptors; growth /development; inflammation; inhibitor /antagonist; lung alveolus; lung injury; premature infant animal; pulmonary circulation; sheep

DESCRIPTION (provided by applicant): This proposal describes a 5 year program for fostering development of an academic career to an independent investigator. The principal investigator for this proposal has completed fellowship in Neonatal-Perinatal medicine and is currently a full time faculty member of the division. The focus of the research is on studying the mechanisms of inhibition of vascular and alveolar development caused by antenatal inflamation which is strongly associated with preterm births and bronchopulmonary dysplasia. The program will enhance the understanding of mechanisms of lung development and vascular biology in the developing fetus. Vascular development and alveolar development are inhibited in preterm infants with bronchopulmonary dysplasia and in preterm animal models of chronic lung injury induced by mechanical ventilation and exposure to oxygen. This laboratory has previously shown that preterm lambs exposed to antenatal inflammation have inhibited alveolarization. This proposal tests the hypothesis that induction of IP-10 (a y-interferon inducible CXC chemokine) and activation of IEP-10 receptor CXCR3 are critical mediators of antenatal inflammation induced inhibition of pulmonary vascular and alveolar development in the preterm. lamb. The specific aims include 1) To establish the optimum time of injection of intraamniotic endotoxin to induce inhibited vascular development in preterm lamb 2) To study the effects of in utero intra-tracheal infusion of recombinant sheep IP-10 on vascular and alveolar development and 3) To inhibit antenatal inflammation induced lung injury response by blocking antenatal EP-10 signaling via inhibition of its receptor CXCR3. The research work will be conducted under the supervision of Dr. Jobe and co-mentors who are all recognized experts in different aspects of pulmonary biology. The Children's Hospital Research Foundation and the Division of Pulmonary Biology provides an ideal setting in which to conduct the proposed research program because of the abundant resources and wide ranging expertise of a talented group of investigators. The experimental design in this proposal incorporates challenging but, particularly in this environment achievable goals that will provide important knowledge in the pathogenesis of bronchopulmonary dysplasia.

描述（由申请人提供）： 该提案描述了一个为期 5 年的计划，旨在促进独立研究者的学术职业发展。 该提案的主要研究者已完成新生儿-围产期医学研究，目前是该部门的全职教员。 该研究的重点是研究产前炎症抑制血管和肺泡发育的机制，该炎症与早产和支气管肺发育不良密切相关。 该计划将增进对发育中胎儿的肺部发育和血管生物学机制的理解。 患有支气管肺发育不良的早产儿以及机械通气和暴露于氧气引起的慢性肺损伤的早产动物模型中，血管发育和肺泡发育受到抑制。 该实验室此前已表明，暴露于产前炎症的早产羔羊会抑制肺泡形成。 该提案检验了以下假设：IP-10（一种 γ-干扰素诱导型 CXC 趋化因子）的诱导和 IEP-10 受体 CXCR3 的激活是产前炎症诱导的早产期肺血管和肺泡发育抑制的关键介质。羊肉。 具体目标包括 1) 确定羊膜内注射内毒素以诱导早产羔羊血管发育受到抑制的最佳时间 2) 研究重组绵羊 IP-10 宫内气管内输注对血管和肺泡发育的影响 3) ) 通过抑制其受体 CXCR3 来阻断产前 EP-10 信号传导，从而抑制产前炎症诱导的肺损伤反应。 研究工作将在乔布博士和共同导师的监督下进行，他们都是肺生物学不同方面的公认专家。 儿童医院研究基金会和肺生物学部门拥有丰富的资源和才华横溢的研究人员团队的广泛专业知识，为开展拟议的研究项目提供了理想的环境。 该提案中的实验设计包含具有挑战性但特别是在这种环境下可实现的目标，这将为支气管肺发育不良的发病机制提供重要的知识。