中国实验动物学报2024，Vol.32Issue(6)：762-771,10.DOI:10.3969/j.issn.1005-4847.2024.06.009
异鼠李素通过抑制LncRNA-gm33782减轻AKI肾小管炎性细胞凋亡
Isorhamnetin alleviates acute kidney injury renal tubular inflammatory cell apoptosis by inhibiting LncRNA-gm33782
摘要
Abstract
Objective To investigate the role of LncRNA-gm33782 in tubular injury in acute kidney injury(AKI)and the mechanism by which isorhamnetin ameliorates inflammatory cell apoptosis of tubular cells in AKI.Methods Forty-eight male C57BL/6J mice were randomly assigned to four groups:control group,AKI model group,electroporation+AKI group,and treatment group(oral administration of 30 mg/kg isorhamnetin).AKI was induced by a one-time intraperitoneal injection of 20 mg/kg cisplatin.Chromatin isolation by RNA purification was used to capture the LncRNA-gm33782 binding protein in AKI-affected kidneys for mass spectrometry,revealing the direct target protein of LncRNA-gm33782.The role of LncRNA-gm33782 in AKI was evaluated by observing the renal function,pathological structure,and expression of renal inflammatory factors(interleukin-1β,interleukin-6,and tumor necrosis factor-α)in mice after electrotransfection and isorhamnetin treatment.Nuclear factor-κB was detected as a critical mediator of inflammation.The expression levels of Bax and Bcl-2 protein were detected and flow cytometry was performed to evaluate the therapeutic effect of isorhamnetin on tubular cell apoptosis in AKI.Results Kidneys with cisplatin-induced AKI showed severe renal tubule injury,macrophage infiltration,and inflammation.Isorhamnetin treatment and LncRNA-gm33782 electrotransfection knockdown alleviated these signs of AKI.LncRNA-gm33782 was mainly expressed in renal tubular cells with AKI.LncRNA-gm33782 binding protein was detected by mass spectrometry,and complement factor H was found to have a direct binding relationship with LncRNA-gm33782.After LncRNA-gm33782 was overexpressed in vitro,the expression of complement factor-H immediately increased,and the therapeutic effect of isorhamnetin on apoptosis of AKI-affected inflammatory cells was inhibited.Conclusions Isorhamnetin alleviates apoptosis of tubular inflammatory cells in AKI by inhibiting the regulatory effect of LncRNA-gm33782 on complement factor H.关键词
急性肾损伤/LncRNA-gm33782/肾原位电转染/异鼠李素/炎性凋亡Key words
acute kidney injury/LncRNA-gm33782/renal in situ electroporation/isorhamnetin/inflammatory cell apoptosis分类
生物科学引用本文复制引用
贾建,谭睿陟,钟霞,粟宏伟,王丽..异鼠李素通过抑制LncRNA-gm33782减轻AKI肾小管炎性细胞凋亡[J].中国实验动物学报,2024,32(6):762-771,10.基金项目
西南医科大学应用基础项目(2021ZKQN120),西南医科大学(2023ZYYQ08),泸州市科技局创新苗子项目(2021-RCM-118),四川省科技厅项目(2022YFS0621).Funded by Application Foundation Project of Southwest Medical University(2021ZKQN120),Southwest Medical University(2023ZYYQ08),Luzhou Science and Technology Bureau Innovative Seedling Project(2021-RCM-118),Project of Science and Technology Department of Sichuan Province(2022YFS0621). （2021ZKQN120）
