脂肪酸结合蛋白4（FABP4）在急性肾损伤向慢性肾脏病进展中的作用与机制研究

急性肾损伤（AKI）作为临床常见病，其修复不良是慢性肾脏病（CKD）患病率上升的重要危险因素。既往研究表明，肾小管上皮细胞在AKI向CKD进展中发挥关键作用。课题组前期研究已证实，脂肪酸结合蛋白FABP4作为胞内重要因子调控内质网应激启动的炎症和凋亡参与AKI的发生。同时我们在顺铂致肾损伤的预实验中也发现，FABP4在受损的肾小管上皮细胞持续上调，而基因敲除或药理抑制FABP4可改善急性肾功能紊乱，延缓肾脏纤维化，但其机制有待揭示。据此本项目提出假说：FABP4在AKI向CKD进展中具有重要作用，肾小管上皮细胞FABP4通过调控内质网应激介导的细胞凋亡参与AKI发生和发展。本项目拟利用肾小管上皮细胞系和FABP4条件敲除小鼠，结合siRNA、腺病毒过表达等细胞和分子生物学技术，阐明FABP4在顺铂致AKI向CKD进展中的作用和机制，为疾病的防治提供新的靶点。

Acute kidney injury (AKI) is a common clinical disease, and its incomplete repair is an important risk factor for the increased prevalence of chronic kidney disease (CKD). Previous studies have shown that renal tubular epithelial cells play a key role in the progression of AKI to CKD. Our previous research has confirmed that fatty acid binding protein FABP4, as an important intracellular factor, regulates inflammation and apoptosis initiated by endoplasmic reticulum stress and participates in the occurrence of AKI. Meanwhile, in the pre-experiment of cisplatin-induced renal injury, we also found that FABP4 was continuously up-regulated in damaged renal tubular epithelial cells, while gene knockout or pharmacological inhibition of FABP4 could improve acute renal dysfunction and delay renal fibrosis, but the mechanism remains to be revealed. We therefore hypothesize that FABP4 plays an important role in the progression of AKI to CKD, and FABP4 in renal tubular epithelial cells participates in the occurrence and development of AKI by regulating apoptosis mediated by endoplasmic reticulum stress. We plan to use renal tubular epithelial cell line and FABP4 conditional knockout mice, combined with cellular and molecular biological techniques such as siRNA and adenovirus overexpression, to clarify the role and mechanism of FABP4 in cisplatin-induced AKI to CKD progression, so as to provide a new target for disease prevention and treatment.