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。

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.