山东医药2025，Vol.65Issue(9)：40-45,6.DOI:10.3969/j.issn.1002-266X.2025.09.009
环状RNA 0006750靶向调控微小RNA-876-3p对脓毒性相关急性肾损伤的影响
Effect of circular RNA 0006750 regulating miR-876-3p on sepsis-associated acute kidney injury
摘要
Abstract
Objective To investigate whether circular RNA 0006750(circ_0006750)influences the progression of sepsis-associated acute kidney injury(SAKI)by targeting microRNA-876-3p(miR-876-3p).Methods Human kidney cortical proximal tubule epithelial cells(HK2)were cultured for 24 h with LPS at concentrations of 0,2.5,5,and 10 μg/mL to establish the SAKI models.Real-time quantitative PCR was used to measure the expression levels of circ_0006750 and miR-876-3p in cells treated with each LPS concentration.Spearman correlation analysis was performed to assess the re-lationship between circ_0006750 and miR-876-3p.Additionally,10 μg/mL LPS-induced SAKI model cells were divided into six groups and transfected with sh-NC vector(interference control group),sh-circ_0006750 vector(circ_0006750 in-terference group),sh-circ_0006750 vector+miR-876-3p inhibitor(circ_0006750 and miR-876-3p co-interference group),NC-OE vector(overexpression control group),circ_0006750-OE vector(circ_0006750 overexpression group),and circ_0006750-OE vector+miR-876-3p mimic(circ_0006750 and miR-876-3p co-overexpression group).Cell prolif-eration was assessed using CCK-8 assay at 24,48,and 72 h of culture.Apoptosis in each group was observed using flow cytometry,and tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,reactive oxygen species(ROS),and malondialdehyde(MDA)levels were measured in each group.The targeted relationship between circ_0006750 and miR-876-3p in HK2 cells was validated using luciferase reporter gene and RNA pull-down assays.Results With the increas-ing concentrations of LPS,the relative expression of circ_0006750 in HK2 cells decreased,while the relative expression of miR-876-3p increased(both P<0.05).In the SAKI model,the expression of circ_0006750 and miR-876-3p showed a negative correlation(r=-0.795,P=0.015).Compared with the interference control group,the circ_0006750 interfer-ence group exhibited decreased OD values at 24,48,and 72 h of culture,increased apoptosis rate,and elevated levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the circ_0006750 interference group,the circ_0006750 and miR-876-3p co-interference group exhibited increased OD values at 24,48,and 72 h,decreased apop-tosis rate,and reduced levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the overex-pression control group,the circ_0006750 overexpression group exhibited elevated OD values at 24,48,and 72 h,re-duced apoptosis rate,and decreased levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the circ_0006750 overexpression group,the circ_0006750 and miR-876-3p co-overexpression group exhibited de-creased OD values at 24,48,and 72 h,increased apoptosis rate,and elevated levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).The circ_0006750 directly interacted with miR-876-3p and suppressed its expression through sponge adsorption.Conclusion The circ_0006750 may promote HK-2 cell proliferation,suppress apoptosis,in-flammatory response,and oxidative stress by targeting miR-876-3p,thereby delaying the progression of SAKI.关键词
环状RNA 0006750/微小RNA-876-3p/脓毒性相关急性肾损伤/炎症反应/氧化应激Key words
circular RNA 0006750/miR-876-3p/sepsis-associated acute kidney injury/inflammatory response/oxidative stress分类
医药卫生引用本文复制引用
王会芳,马媛媛,张鑫,陈凯雯,张晓丽,赵建荣,王晓寅..环状RNA 0006750靶向调控微小RNA-876-3p对脓毒性相关急性肾损伤的影响[J].山东医药,2025,65(9):40-45,6.基金项目
河北省医学科学研究课题计划(20250142). （20250142）
