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基于Nrf2/HO-1信号通路研究下调miR-29对慢性心律失常大鼠的干预作用

The effect of down-regulated miR-29 on chronic arrhythmia in rats based on Nrf2/HO-1 signaling pathway
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摘要 目的探讨基于核因子E2相关因子(Nrf)2/血红素氧合酶(HO)-1信号通路研究下调微小RNA(miR)-29对慢性心律失常大鼠的干预作用。方法选取40只健康雄性大鼠,10只为正常组,其余30只建立慢性心律失常模型,分为模型组、上调组、下调组,4组分别干预。对各组心肌组织进行苏木素-伊红(HE)染色,采用酶联免疫吸附试验检测血浆抗人脑N端B型钠尿肽前体(NT-proBNP)水平,多普勒超声测定左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)水平变化,无创血流动力学检测收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、心率(HR)。结果与正常组对比,模型组、上调组Nrf2、HO-1、miR-29表达显著上升,下调组Nrf2表达显著下降,miR-29、HO-1表达显著升高(均P<0.05);与模型组对比,上调组HO-1、Nrf2、miR-29表达显著升高,下调组Nrf2、miR-29表达显著下降,HO-1表达显著上升(P<0.05);与上调组对比,下调组Nrf2、miR-29、HO-1表达显著下降(均P<0.05)。与正常组相比,模型组、上调组、下调组SBP、DBP、MAP、HR、LVEF水平明显降低,NT-proBNP、LVESD、LVEDD明显升高(均P<0.05);与模型组相比,上调组、下调组SBP、DBP、MAP、HR水平明显升高,上调组心功能指标明显升高,下调组LVESD、LVEDD、NT-proBNP水平明显降低、LVEF水平明显升高(均P<0.05);与上调组相比,下调组SBP、DBP、MAP、HR、LVEF水平明显升高,NT-proBNP、LVESD、LVEDD水平明显降低(均P<0.05)。结论下调miR-29表达可有效改善慢性心律失常大鼠心功能及血流动力学指标,保护心脏,其机制可能与激活Nrf2/HO-1通路相关。 Objective To investigate the intervention effect of down-regulated miRNA(miR)-29 on chronic arrhythmia in rats based on nuclear factor E2-related factor(Nrf)2/heme oxygenase(HO)-1 signaling pathway.Methods Forty healthy male rats were selected,10 of them were in the normal group,and the other 30 were established into chronic arrhythmia model.Rats were divided into model group,up-regulation group and down-regulation group.The four groups were intervened respectively.The myocardial tissue in each group was stained with hematoxylin-eosin(HE).The plasma level of anti human brain N-terminal Pro-brain natriuretic peptide(NT-proBNP)was detected by enzyme-linked immunosorbent assay.The left ventricular end systolic diameter(LVESD),end diastolic diameter of the left ventricular(LVEDD)and left ventricular ejection fraction(LVEF)were measured by doppler ultrasound,systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP)and heart rate(HR)were measured by noninvasive hemodynamics.Results Compared with normal group,the expressions of HO-1,Nrf2,miR-29 were significantly increased in model group and up-regulated group,the expressions of Nrf2 and miR-29 were significantly decreased and the expression of HO-1 was significantly increased in down-regulated group(all P<0.05).Compared with model group,the expressions of HO-1,Nrf2,miR-29 were significantly increased in up-regulated group,the expressions of Nrf2 and miR-29 were significantly decreased and the expression of HO-1 was significantly increased in down-regulated group(all P<0.05).Compared with up-regulated group,the expressions of Nrf2,miR-29,HO-1 were significantly decreased in down-regulated group(all P<0.05).Compared with normal group,the levels of SBP,DBP,MAP,HR and LVEF were significantly decreased and the levels of NT-proBNP,LVESD and LVEDD were significantly increased in model group,up-regulated group and down-regulated group(all P<0.05).Compared with model group,the levels of SBP,DBP,MAP and HR were significantly increased in up-regulated
作者 郑丽玮 黄晶 雷玉华 华晓芳 朱贤林 周慧 ZHENG Li-Wei;HUANG Jing;LEI Yu-Hua(Cardiovascular Center,Enshi Tujia Autonomous Prefecture Central Hospital,Enshi 445000,Hubei,China)
出处 《中国老年学杂志》 CAS 北大核心 2024年第4期867-871,共5页 Chinese Journal of Gerontology
基金 国家自然科学基金项目(No.81760257)。
关键词 核因子E2相关因子2 血红素氧合酶-1 微小RNA-29 慢性心律失常 Nuclear factor E2 related factor 2 Heme oxygenase-1 miR-29 Chronic arrhythmia
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