IGFBP7对脓毒症小鼠肾小管上皮细胞分裂周期的影响及其机制研究

项目名称： IGFBP7对脓毒症小鼠肾小管上皮细胞分裂周期的影响及其机制研究

项目编号： No.81501646

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： 王晓琳

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 尿液IGFBP7可作为急性肾损伤 (AKI) 早期诊断最重要的标记物之一，但机制不清。项目组前期研究发现脓毒症AKI小鼠肾小管上皮细胞IGFBP7表达明显升高，且细胞分裂周期停滞于G0-G1。另有研究显示，IGFBP7可促进肿瘤细胞的衰老和凋亡。我们推测IGFBP7可能在脓毒症AKI时通过调控肾小管上皮细胞分裂周期，从而影响肾小管上皮细胞的损伤修复。本研究拟观察实验小鼠在脓毒症不同时期IGFBP7与肾小管上皮细胞分裂周期之间的关系；培养人肾小管上皮细胞，利用siRNA使其IGFBP7表达静止，予BRAF-MEK-ERK通路抑制物预处理，再予LPS刺激，观察肾小管上皮细胞分裂相关蛋白水平的变化；检测脓毒症患者血、尿样IGFBP7水平与AKI临床指标相关性。通过以上研究，在分子、细胞、动物及临床层面探索IGFBP7影响人肾小管上皮细胞分裂周期及损伤修复的机制，及对AKI的预警和预后作用。

中文关键词： 脓毒症；急性肾损伤；肾小管上皮细胞；细胞周期；胰岛素结合蛋白7

英文摘要： Urine IGFBP7 increased obviously in acute kidney injury(AKI) patients and was considered to be a marker for AKI, however, the reason and mechanism were still uncovered.Our pre-experiment had suggested IGFBP7 expession was increased in renal tubular epithelial cells of sepsis mice,which was positive corelated to serum creatinine, and renal cell division cycle was ceased at stage G0/G1 simutaneously. As renal tubule epithelium injury is common in septic AKI. So our hypothesis is that IGFBP7 might control kidney epithelium cell cycle in septic AKI and play an important role in kidney epithelium injury and repair. We plan to observe the relationship of IGFBP7 level and kindey tubule epithelium cell cycle in different stage of sepsis mice. And then silence IGFBP7 gene in human kidney tubule epithelium cell line by siRNA technology. After pre-conditioned with inhibitor of BRAF-MEK-ERK, kidney tubule epithelium is stimulated with LPS or serum of sepsis patients. Epithelium cell cycle and related proteins were obsereved. Finally,the correlation between blood/urine IGFBP7 levels and clinical index for AKI was also detected.Our objective is identifying the role of IGFBP7 in cell division cycle of idney tubule epithelium and epithelium repair ,and the clinical value for predicting the develepment and prognosis of AKI.

英文关键词： sepsis;acute kidney injury;renal tubule epithelium;cell cycle;IGFBP7