Renal denervation alleviates renal ischemic reperfusion injury-induced acute and chronic kidney injury in rats partly by modulating miRNAs
Renal denervation alleviates renal ischemic reperfusion injury-induced acute and chronic kidney injury in rats partly by modulating miRNAs
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肾去神经支配部分通过调节 miRNA 减轻大鼠肾缺血再灌注损伤引起的急性和慢性肾损伤
DOI：
10.1007/s10157-021-02129-1
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发表时间：
2021-08
影响因子：
2.3
通讯作者：
Jie Sun
中科院分区：
文献类型：
--
作者：
Xiangyu Zou;Sihao Lin;Liang Zhong;Jie Liu;Yu Meng;Yingjian Zhu;Jie Sun
背景肾去神经支配（renal denervation，RDN）可促进肾损伤的修复，而miRNAs参与了肾损伤的病理生理过程。然而，RDN后miRNA的改变及相关保护机制仍有待进一步研究。方法建立肾缺血再灌注损伤（IRI）大鼠模型，进行RDN。分别于术后24 h和2周处死动物。在24 h时检测酪氨酸羟化酶（TH）水平、肾功能、肾小管细胞凋亡和组织学切片，而在2周时评估肾纤维化和毛细血管。此外，采用微阵列技术检测损伤肾组织中miRNAs的表达，并对靶基因进行分析。ResultsWe发现去神经组24 h时TH被清除，肾功能得到改善。RDN可减少肾小管上皮细胞凋亡，减轻组织学损害。此外，2周后观察到毛细血管密度增加和肾纤维化减轻。此外，RDN治疗后，miRNAs的数量上调，且miRNAs靶向促血管生成、抗纤维化和炎症通路。结论RDN是一种可靠的方法，可减轻IR诱导的急性和慢性肾损伤，并调节参与此过程的miRNAs相关的促血管生成、抗纤维化或炎症通路。
BackgroundRenal denervation (RDN) has been used to promote kidney injury repair, whereas miRNAs have been found to be involved in the pathophysiology of renal injury. However, the miRNA alterations that occur after RDN and the related protective mechanisms remain to be determined.MethodsRenal ischemic reperfusion injury (IRI) rat model was established and RDN was performed. Animals were killed at 24 h and 2 weeks following the operation. Tyrosine hydroxylase (TH) levels, renal function, tubular cell apoptosis and histological sections were examined at 24 h, whereas renal fibrosis and capillary vessels were assessed at 2 weeks. Furthermore, the expression of miRNAs in the injured kidney was determined using micro-array and the target genes were analyzed.ResultsWe found that TH was eliminated and that renal function was improved in the denervation group at 24 h. RDN reduced tubular cell apoptosis and mitigated the histological lesion. Furthermore, an increase of capillary vessel density and reduction of renal fibrosis were observed after 2 weeks. Moreover, the numbers of miRNAs were up-regulated after RDN treatment, and the miRNAs targeted pro-angiogenic, anti-fibrotic and inflammatory pathways.ConclusionsRDN is a reliable method for alleviating IRI-induced acute and chronic kidney injury, and modulating the miRNA-related pro-angiogenic, anti-fibrotic or inflammatory pathways involved in this process.
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