Fractalkine/CX3CR1增加老年急性缺血性肾损伤易感性的机制研究

项目名称： Fractalkine/CX3CR1增加老年急性缺血性肾损伤易感性的机制研究

项目编号： No.81501194

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 宁一纯

作者单位： 复旦大学

项目金额： 17.5万元

中文摘要： 急性肾损伤（AKI）是常见的急危重症，老年人是AKI的重要发病人群。近年研究证实，机体内环境影响衰老器官的组织重塑和功能，但内环境影响老年AKI发生发展的机制尚不清楚。我们前期构建了连体动物模型并应用于肾脏衰老，发现异龄连体中老年小鼠肾脏的衰老相关性指标有改善趋势，凋亡水平降低，自噬水平增高；并发现内环境因子Fractalkine与肾脏衰老密切相关。为此，我们提出科学假说：Fractalkine/CX3CR1可能通过影响凋亡、自噬、炎症等信号通路增加老年缺血性AKI的易感性。为验证这一假说，本课题将在连体小鼠模型基础上构建缺血性AKI模型，采用基因敲除鼠、免疫组化、RT-PCR、western blot等手段，从动物整体水平、组织、细胞、分子等多方面探讨Fractalkine/CX3CR1在增加老年缺血性AKI易感性中的作用及其机制，从而完善老年AKI发病机制，寻找防治老年AKI的新靶点。

中文关键词： 肾脏衰老；急性肾损伤；连体模型；内环境；Fractalkine

英文摘要： Acute Kidney Injury (AKI) is a common and important critical case in clinic, and the geratic people are the major morbidity population of AKI. Recent studies have confirmed that the impact of internal environment on tissue remodeling and function changing of aging organ, but whether the internal environment affecting the development of senile AKI is unclear. In previous study, we constructed heterochronic parabioses models to study kidney senescence and dentified the difference internal milieu factors between young – old by high-throughput genomics technology. We have found fractalkine is closely related to kidney senescence. So, we propose scientific hypothesis: Fractalkine/CX3CR1 may influence apoptosis, autophagy, inflammation and other signaling pathways to increase the susceptibility of elderly ischemic AKI. To test this hypothesis, this study will build ischemic AKI models based on the heterochronic parabioses models, using knockout mice, immunohistochemistry, RT-PCR, western blot and other means, from the whole animal level, organizations, cellular, molecular, to discuss how Fractalkine/CX3CR1 increase the susceptibility of elderly ischemic AKI and what the mechanism is. Our research will enrich the development of aged AKI theory and expound a new target for prevention and treatment of AKI in elderly patients.

英文关键词： kidney senescence;acute kidney injury;parabiosis model;internal milieu;Fractalkine