TIMP-2和IGFBP-7早期预测急性肾损伤作用机制的研究进展  

Research progress on mechanism of action of early prediction in acute kidney injury by tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7

作　　者：徐凤娇 张宇 杨玉兰[2] XU Fengjiao;ZHANG Yu;YANG Yulan(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin300250,China;Department of Nephrology and Rheumatology,the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin300140,China)

机构地区：[1]天津中医药大学研究生院,天津300250 [2]天津中医药大学第二附属医院肾病风湿科,天津300140

出　　处：《中国医药导报》2024年第19期56-61,共6页China Medical Herald

基　　金：天津市教委科研计划项目(2021KJ158)。

摘　　要：严重感染、缺血缺氧等导致急性肾损伤,使肾脏血管受损、肾小管中炎症细胞和促炎性细胞因子释放增多、糖酵解过程触发并上调。其中炎症细胞增多和血管受损导致小分子核糖核苷酸表达减少,从而上调小管上皮细胞中基质金属蛋白酶。金属蛋白酶组织抑制因子-2(TIMP-2)可广泛抑制基质金属蛋白酶活性(优先与基质金属蛋白酶2结合),为恢复两者的动态平衡,TIMP-2表达增多,同时促炎性细胞因子可直接使小管上皮细胞分泌TIMP-2。转化生长因子β1参与急性肾损伤时胰岛素样生长因子结合蛋白-7(IGFBP-7)增多的过程。IGFBP-7可延长胰岛素、胰岛素样生长因子1半衰期,促进其与受体结合,延长相关通路的激活,并催化酪氨酸蛋白激酶活性,使磷酸果糖激酶活性提高,最终引起急性肾损伤肾小管上皮细胞中糖酵解过程激活、通量增多。TIMP-2与IGFBP-7能加重细胞周期停滞,可作为急性肾损伤细胞周期停滞的标志物。Severe infections,ischemia and hypoxia can lead to acute kidney injury,causing damage to renal blood vessels,increased release of inflammatory cells and pro-inflammatory cytokines in renal tubules,and triggering and upregulation of glycolysis processes.Increase of inflammatory cells and vascular damage lead to decrease in the expression of small molecule ribonucleotides,thereby upregulating matrix metalloproteinases in tubular epithelial cells.Tissue inhibitor of metalloproteinase 2(TIMP-2)can widely inhibit activity of matrix metalloproteinases(priority binding to matrix metalloproteinase 2),in order to restore dynamic balance between the two,expression of TIMP-2 increased,simultaneously,pro-inflammatory cytokines can directly induce secretion of TIMP-2 by tubular epithelial cells.Transforming growth factorβ1 is involved in increase of insulin-like growth factor binding protein 7(IGFBP-7)during acute kidney injury.IGFBP-7 can prolong half-life of insulin and insulin-like growth factor 1,promote their binding to receptors,prolong activation of related pathways,and catalyze tyrosine protein kinase activity,leading to increased activity of phosphofructokinase and ultimately causing activation and increased flux of glycolysis in acute renal injury renal tubular epithelial cells.TIMP-2 and IGFBP-7 can aggravate cell cycle arrest and can be used as markers of cell cycle arrest in acute kidney injury.

关 键 词：急性肾损伤 标志物 基质金属蛋白酶 金属蛋白酶组织抑制因子2 胰岛素样生长因子结合蛋白7 

分 类 号：R692[医药卫生—泌尿科学]