首页|miR-302a-3p靶向调节FGF19/GSK-3β/Nrf2通路减轻缺氧/复氧诱导的心肌细胞损伤

miR-302a-3p靶向调节FGF19/GSK-3β/Nrf2通路减轻缺氧/复氧诱导的心肌细胞损伤

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目的:探讨miR-302a-3p靶向调节成纤维细胞生长因子19(FGF19)/糖原合成酶激酶-3β(GSK-3β)/核因子E2相关因子2(Nrf2)通路对缺氧/复氧(H/R)诱导的心肌细胞损伤的影响.方法:将H9C2细胞分为Ctrl组、H/R 组、inhibitor NC 组、miR-302a-3p inhibitor 组、miR-302a-3p inhibitor+si-NC 组、miR-302a-3p inhibitor+ si-FGF19 组,检测miR-302a-3p表达、细胞增殖(OD450)、凋亡、活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平及FGF19、p-GSK-3β、核Nrf2、Bcl-2相关X蛋白(Bax)、半胱氨酸蛋白酶3(caspase-3)蛋白表达变化并探究miR-302a-3p与FGF19的关系.结果:与Ctrl组比较,H/R组H9C2细胞中miR-302a-3p、细胞凋亡率、ROS、MDA水平、Bax、caspase-3、p-GSK-3β蛋白表达升高,FGF19、核Nrf2 蛋白表达、OD450 值、SOD水平降低(P<0.05);与inhibitor NC组比较,miR-302a-3p inhibitor组对应指标变化趋势与上述相反(P<0.05);si-FGF19减弱了下调miR-302a-3p对H/R诱导的心肌细胞损伤的保护作用.结论:下调miR-302a-3p可通过靶向激活FGF19/GSK-3β/Nrf2通路减轻H/R诱导的心肌细胞损伤.
miR-302a-3p targets the regulation of FGF19/GSK-3 beta/Nrf2 pathway to alleviate hypoxia/reoxygenation-induced cardiomyocyte injury
Objective:To investigate the influence of miR-302a-3p on myocardial cell injury induced by hy-poxia/reoxygenation by targeting the regulation of fibroblast growth factor 19(FGF19)/glycogen syn-thase kinase-3 beta(GSK-3β)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway.Methods:H9C2 cells were separated into the control(Ctrl)group,H/R group,inhibitor negative control(NC)group,miR-302a-3p inhibitor group,miR-302a-3p inhibitor+si-NC group,and miR-302a-3p inhibi-tor+si-FGF19 group.The levels of miR-302a-3p expression,cell proliferation(OD450),apoptosis,re-active oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA)levels and FGF19,p-GSK-3β,nuclear Nrf2,Bcl-2-related X protein(Bax),and cysteine protease 3(caspase-3)protein expression were detected,and the relationship between miR-302a-3p and FGF19 was ex-plored.Results:Compared with those in the Ctrl group,the miR-302a-3p,apoptosis rate,ROS,MDA levels,Bax,caspase-3,p-GSK-3β protein expression in H9C2 cells in the H/R group in-creased,the FGF19 and nuclear Nrf2 protein expression,OD450 value,and SOD level decreased(P<0.05);Compared with those the inhibitor NC group,the changing trend of the corresponding indica-tors in the miR-302a-3p inhibitor group was opposite to the above(P<0.05);si-FGF19 attenuated the protective effect of down-regulated miR-302a-3p against H/R-induced cardiomyocyte injury.Conclu-sion:Down-regulation of miR-302a-3p can alleviate H/R-induced cardiomyocyte injury by targeting the activation of FGF19/GSK-3β/Nrf2 pathway.

miR-302a-3pHypoxia/ReoxygenationApoptosis

张雅静、刘永顺、田凤石

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天津市公安医院心内科 天津 300040

miR-302a-3p 缺氧/复氧 凋亡

天津市科技发展计划项目

2018-HBCD-18

2024

武汉大学学报(医学版)
武汉大学

武汉大学学报(医学版)

CSTPCD
影响因子:0.959
ISSN:1671-8852
年,卷(期):2024.45(3)
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