缺血预适应介导miR-376c-3p促进血管修复与新生对肾缺血再灌注损伤后的保护作用及机制

Renal ischemia reperfusion injury (IRI) is still a clinical urgent problem to be solved, and Ischemic preconditioning (IPC) can improve the renal IRI in rats, whereas the underlying mechanisms are not completely understood. Based on our previous experiments, we found that IPC could significantly increase the expression levels of vascular endothelial growth factor (VEGF) to promote the microvascular endothelial repair and angiogenesis, thus to protect renal IRI. Bioinformatics analyses and luciferase-reporter assay showed that miR-376c-3p targeted the 3′-UTR of VEGF mRNA. Therefore, our data suggested that IPC might decreased miR-376c-3p regulation by VEGF to promote the microvascular endothelial repair and angiogenesis, thus to relieve the occurrence of renal IRI. This project will use Immunoprecipitation and Electrophoretic mobility shift assay in molecular biology, cytology, and animal models, to observe the effect of IPC on the expression of VEGF and its related genes, to determine the regulation of miR-376c-3p by IPC, to clarify whether IPC can regulate miR-376c-3p by VEGF, to promote renal microvascular endothelial repair and angiogenesis, thus providing a new theoretical basis for the protection after renal IRI.

肾脏缺血再灌注损伤（IRI）是临床常见且亟待解决的问题，缺血预适应（IPC）可有效减轻肾脏IRI，但具体机制尚不明确。我们前期研究表明：IPC可显著增加局部血管内皮生长因子（VEGF），促进缺血肾微血管修复与新生，从而对肾脏产生保护作用。生物信息学和荧光素酶报告基因结果表明miR-376c-3p可与VEGF mRNA的3′-UTR位点结合。因此, 我们推测：IPC可介导miR-376c-3p调控VEGF，促进缺血肾微血管修复及血管新生，进而减轻其IRI。本项目将采用免疫沉淀、凝胶电泳迁移率等实验，从分子、细胞以及动物实验等多层次，明确IPC调控VEGF及其相关基因表达的作用；确定IPC对miR-376c-3p的调控；阐明IPC通过miR-376c-3p调控VEGF的表达，促进缺血肾微血管修复及新生的机制，为肾脏IRI后的修复提供新的理论依据。

肾脏缺血再灌注损伤（IRI）是临床常见且亟待解决的问题，缺血预适应（IPC）可有效减轻肾脏IRI，但具体机制尚不明确。我们前期研究表明：IPC可显著增加局部血管内皮生长因子（VEGF），促进缺血肾微血管修复与新生，从而对肾脏产生保护作用。生物信息学和荧光素酶报告基因结果表明miR-376c-3p可与VEGF mRNA的3′-UTR位点结合。因此, 我们推测：IPC可介导miR-376c-3p调控VEGF，促进缺血肾微血管修复及血管新生，进而减轻其IRI。本项目采用免疫沉淀、凝胶电泳迁移率等实验，从分子、细胞以及动物实验等多层次，明确IPC调控VEGF及其相关基因表达的作用；确定IPC对miR-376c-3p的调控；阐明IPC通过miR-376c-3p调控VEGF的表达，促进缺血肾微血管修复及新生的机制，为肾脏IRI后的修复提供新的理论依据。