首页|高良姜素通过调节miR-124/STAT3轴对动脉粥样硬化大鼠血管内皮细胞损伤的影响

高良姜素通过调节miR-124/STAT3轴对动脉粥样硬化大鼠血管内皮细胞损伤的影响

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目的 探讨高良姜素通过调节微RNA124(miR-124)/信号转导与转录激活因子3(STAT3)轴对动脉粥样硬化(AS)大鼠血管内皮细胞损伤的影响。方法 研究时间为2023年1―5月,原代培养大鼠胸主动脉内皮细胞分为对照组(未做任何处理)、模型组(80 mg/L ox-LDL处理)、高良姜素组(50 μmol/L高良姜素+80 mg/L ox-LDL处理)、高良姜素+inhibitor NC组(50 μmol/L高良姜素+80 mg/L ox-LDL处理后转染inhibitor NC)、高良姜素+miR-124 inhibitor组(50 μmol/L高良姜素+80 mg/L ox-LDL处理后转染miR-124 inhibitor)。双萤光素酶报告基因实验验证miR-124、STAT3靶向关系;实时荧光定量逆转录聚合酶链式反应(qRT-PCR)检测miR-124表达;蛋白质印迹法检测STAT3蛋白表达;MTT法测定细胞增殖;流式细胞术检测细胞凋亡;酶联免疫吸附测定(ELISA)检测炎症因子以及一氧化氮(NO)、活性氧(ROS)水平。结果 miR-124靶向调控STAT3表达。与对照组相比,模型组miR-124水平(1。00±0。00 比0。45±0。06)、D(λ)490 值(0。98±0。13 比0。44±0。05)显著下降(P<0。05),凋亡率[(5。58±0。68)%比(15。83±2。06)%]、STAT3水平(0。48±0。05 比1。08±0。13)、IL-1β[(12。05±1。17)mg/L比(22。42±2。36)mg/L]、IL-6[(4。13±0。48)mg/L比(9。64±0。98)mg/L]、TNF-α[(2。11±0。25)mg/L比(6。63±0。66)mg/L]、NO[(22。26±2。33)μmol/L比(90。25±9。44)μmol/L]、ROS[(32。93±3。52)μmol/L比(60。91±7。19)μmol/L]水平显著升高(P<0。05);与模型组相比,高良姜素组miR-124水平(0。45±0。06比0。89±0。01)、D(λ)490值(0。44±0。05比0。84±0。09)显著升高(P<0。05),凋亡率[(15。83±2。06)%比(6。28±0。72)%]、STAT3水平(1。08±0。13比0。53±0。06)、IL-1β[(22。42±2。36)mg/L比(16。92±1。93)mg/L]、IL-6[(9。64±0。98)mg/L比5。42±0。53)mg/L]、TNF-α[(6。63±0。66)mg/L比(3。57±0。37)mg/L]、NO[(90。25±9。44)μmol/L比(34。84±4。10)μmol/L]、ROS[(60。91±7。19)μmol/L比(30。41±3。05)μmol/L]水平显著下降(P<0。05),下调miR-124抑制高良姜素对AS大鼠血管内皮细胞损伤的改善。结论 高良姜素通过上调miR-124来下调STAT3表达,从而减轻AS大鼠血管内皮细胞损伤。
Effect of galangin on vascular endothelial cell injury in atherosclerotic rats by regulating miR-124/STAT3 axis
Objective To investigate the effect of galangin on vascular endothelial cell injury in atherosclerosis(AS)rats by regulat-ing the micro RNA124(miR-124)/signal transducer and activator of transcription 3(STAT3)axis.Methods The study started from January 2023 and ended in May 2023.Primary cultured rat aortic endothelial cells were grouped into control group(without any treat-ment),model group(80 mg/L ox-LDL treatment),galangin group(50 μmol/L galangin+80 mg/L ox-LDL treatment),galangin+inhibitor NC group(transfected with inhibitor NC after treatment with 50 μmol/L galangin+80 mg/L ox-LDL),galangin+miR-124 inhibitor group(transfected with miR-124 inhibitor after treatment with 50 μmol/L galangin+80 mg/L ox-LDL).The dual luciferase gene reporter assay was applied to verify the targeting relationship between miR-124 and STAT3,real-time fluorescent quantitative reverse transcription polymerase chain reaction(qRT-PCR)to detect miR-124 expression,Western blotting to detect STAT3 protein expression,MTT meth-od to measure cell proliferation,flow cytometry to detect cell apoptosis,and enzyme-linked immunosorbent assay(ELISA)to detect the levels of inflammatory factors,nitric oxide(NO)and reactive oxygen species(ROS).Results MiR-124 targeted and regulated the STAT3 expression.Compared with the control group,the miR-124 level(1.00±0.00 vs.0.45±0.06)and D(λ)490 value(0.98±0.13 vs.0.44±0.05)in the model group were obviously decreased(P<0.05),while the apoptosis rate[(5.58±0.68)%vs.(15.83±2.06)%],STAT3 level(0.48±0.05 vs.1.08±0.13),and the levels of IL-1β[(12.05±1.17)mg/L vs.(22.42±2.36)mg/L],IL-6[(4.13±0.48)mg/L vs.(9.64±0.98)mg/L],TNF-α[(2.11±0.25)mg/L vs.(6.63±0.66)mg/L],NO[(22.26±2.33)μmol/L vs.(90.25±9.44)μmol/L],ROS[(32.93±3.52)μmol/L vs.(60.91±7.19)μmol/L]were obviously increased(P<0.05).Compared with the model group,the miR-124 level(0.45±0.06 vs.0.89±0.01)and D(λ)490 value(0.44±0.05 vs.0.84±0.09)in the galangin group were obviously increased(P<0.05),while the apoptosis rate[(15.83±2.06)%vs.(6.28±0.72)%],and the levels of STAT3(1.08±0.13)vs.(0.53±0.06),IL-1β[(22.42±2.36)mg/L vs.(16.92±1.93)mg/L[,IL-6[(9.64±0.98)mg/L vs.(5.42±0.53)mg/L],TNF-α[(6.63±0.66)mg/L vs.(3.57±0.37)mg/L],NO[(90.25±9.44)μmol/L vs.(34.84±4.10)μmol/L],and ROS[(60.91±7.19)μmol/L vs.(30.41±3.05)μmol/L]were obviously decreased(P<0.05).Down-regula-tion of miR-124 inhibited the improvement of galangin on vascular endothelial cell injury in AS rats.Conclusion Galangin can down-regulate the expression of STAT3 by up-regulating miR-124,thereby alleviating the injury of vascular endothelial cells in AS rats.

AtherosclerosisGalanginMicro RNA124Signal transducer and activator of transcription 3Vascular endothelial cells

齐飞、汪晶、白志峰、宋金玉、白丽

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北京丰台右安门医院神经介入科,北京 100069

动脉粥样硬化 高良姜素 微RNA124 信号转导与转录激活因子3 血管内皮细胞

2025

安徽医药
安徽省药学会

安徽医药

影响因子:1.941
ISSN:1009-6469
年,卷(期):2025.29(2)