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多功能分子SLPI调节肾缺血再灌注损伤和修复的作用及机制

陈飞¹, 吴圆圆², 杨斌^1,3,*

¹南通-莱斯特联合肾脏病学研究所，南通大学附属医院肾内科，南通大学医学院，南通 226001；²南通大学医学院病理系，南通 226001；³莱斯特大学生命科学院心血管科学系肾脏研究组，莱斯特 LE1 9HN，英国

摘要

分泌性白细胞蛋白酶抑制因子(secretory leukocyte protease inhibitor, SLPI)主要由免疫细胞及多种上皮细胞产生，受多种细胞因子调节，如转化生长因子β1、白介素1β和肿瘤坏死因子α等。除公认的抗蛋白酶活性外，近年来发现SLPI还具备抗细胞凋亡、调节细胞周期、促进细胞分化和增殖及抑制炎症反应等多种特性。SLPI亦可增强细胞吞噬功能和免疫系统对病原体/损伤细胞的清除，从而改善组织损伤及启动修复。另外，新近研究表明，血清SLPI水平变化对心血管术后急性肾损伤的发生具有较高的诊断价值，提示SLPI参与肾脏缺血再灌注损伤相关的免疫反应。本文中我们综述了SLPI在不同器官损伤模型中的表达、调控、信号通路机制以及相关生物学事件，并探讨和评价其在缺血再灌注所致急性肾损伤中发挥保护作用及作为生物学标志物的潜力。

关键词： 分泌性白细胞蛋白酶抑制因子; 急性肾损伤; 缺血再灌注损伤; 生物标志物

The role and mechanism of multifunctional molecule SLPI in regulating ischemia- reperfusion induced acute kidney injury and repair

CHEN Fei¹, WU Yuan-Yuan², YANG Bin^1,3,*

¹Nantong-Leicester Joint Institute of Kidney Science, Department of Nephrology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China；²Department of Pathology, Medical School of Nantong University, Nantong 226001, China；³Renal Research Group, Cardiovascular Sciences, University of Leicester, University Hospitals of Leicester, Leicester LE1 7RH, UK

Abstract

The secretory leukocyte protease inhibitor (SLPI) is mainly produced by immune cells and various epithelial cells, and is regulated by a variety of cytokines, such as transforming growth factor β1, interleukin 1β and tumor necrosis factor α. In addition to commonly known anti-protease activity, it has been found in recent years that SLPI plays essential roles in anti-apoptosis, regulating cell cycle, cell differentiation and proliferation, and inhibiting inflammatory response. SLPI can also assist the immune system to clear pathogens/damaged cells by enhancing the phagocytic function of phagocytes, so as to ameliorate tissue damage and promote repair. Moreover, recent studies have shown that the change of SLPI level in the serum of patients post cardiovascular surgery has a high diagnostic value in predicting the occurrence of acute kidney injury, suggesting that SLPI is involved in ischemia-reperfusion (IR) induced acute kidney injury. In this review, we summarized the expression, regulation, signaling pathways and associated biological events of SLPI in different organ injury models, and also discussed and evaluated the potential role of SLPI in renoprotection against IR induced acute kidney injury and its potential as a new biomarker.

Key words: secretory leukocyte protease inhibitor; acute kidney injury; ischemia-reperfusion injury; biomarkers

收稿日期：　　录用日期：

通讯作者：杨斌　　E-mail:

DOI: 10.13294/j.aps.2024.0027

引用本文：

陈飞, 吴圆圆, 杨斌. 多功能分子SLPI调节肾缺血再灌注损伤和修复的作用及机制[J]. 生理学报 2024; 76 (3): 475-486.

CHEN Fei, WU Yuan-Yuan, YANG Bin. The role and mechanism of multifunctional molecule SLPI in regulating ischemia- reperfusion induced acute kidney injury and repair. Acta Physiol Sin 2024; 76 (3): 475-486 (in Chinese with English abstract).