miR-409-3p对川崎病幼鼠心肌损伤的调控作用及机制
Regulatory effects and mechanisms of miR-409-3p on myocardial injury in young rats with Kawasaki disease
通力嘎 1张青山 2吴春霞1
作者信息
- 1. 内蒙古民族大学附属医院 蒙西医结合儿科,通辽 028000
- 2. 内蒙古民族大学附属医院 心血管内二科,通辽 028000
- 折叠
摘要
为研究miR-409-3p通过沉默信息调节因子1(silent information regulator 1,SIRT1)/叉头转录因子O1(forkhead transcription factor O1,FOXO1)信号通路对川崎病(Kawasaki disease,KD)幼鼠心肌损伤的影响,取SD幼年雄性大鼠,随机分为对照组、模型组、miR-409-3p antagomir 组、miR-409-3p antagomir 阴性对照组、EX527(SIRT1 抑制剂,1 μg/kg)组、miR-409-3p antagomir+EX527(1 μg/kg)组,每组 12 只.采用 qRT-PCR 检测大鼠心肌组织 miR-409-3p 表达;ELISA 检测大鼠血清中肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)、心肌肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTnⅠ)、心肌肌钙蛋白T(cardiac troponin T,cTnT)、TNF-α、IL-17、IL-18 水平.结果显示,与模型组、miR-409-3p antagomir+EX527 组分别比较,miR-409-3p antagomir组大鼠心肌组织病理损伤减轻,血清CK-MB、cTnⅠ、cTnT、TNF-α、IL-17及IL-18水平,心肌组织 acely-FOXO1/FOXO1 均降低(P＜0.05),心功能指标左室射血分数(left ventricular ejection fraction,LVEF)、左室缩短分数(left ventricular fractional shortening,LVFS)及心肌组织SIRT1表达均升高(P＜0.05);EX527组大鼠心肌组织病理损伤加重,血清 CK-MB、cTnⅠ、cTnT、TNF-α、IL-17 及 IL-18 水平,心肌组织 acely-FOXO1/FOXO1 均升高(P＜0.05),心功能指标LVEF、LVFS及心肌组织SIRT1表达均降低(P＜0.05).大鼠心肌细胞中miR-409-3p可靶向下调SIRT1表达.该研究提示,miR-409-3p可靶向下调SIRT1表达参与KD幼鼠心肌损伤过程,下调miR-409-3p表达可通过激活SIRT1/FOXO1信号起到抗炎作用,进而减轻KD幼鼠心肌损伤.
Abstract
To study the influence of miR-409-3p on myocardial injury in young mice with Kawasaki disease(KD)through silent information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)signaling pathway,SD juvenile male rats were randomly divided into control group,model group,miR-409-3p antagomir group,miR-409-3p antagomir negative control group,EX527(SIRT1 inhibitor,1 μg/kg)group,and miR-409-3p antagomir+EX527(1 μg/kg)group,12 per group.The expression of miR-409-3p in rat myocardium was detected by qRT-PCR;ELISA was performed to detect levels of creatine kinase isoenzyme(CK-MB),cardiac troponin Ⅰ(cTnⅠ),cardiac troponin T(cTnT),TNF-α,IL-17,IL-18 in serum.The result showed that compared with the model group and the miR-409-3p antagomir+EX527 group,the pathological injuries in myocardial tissue of the miR-409-3p antagomir group were alleviated,the serum CK-MB,cTnⅠ,cTnT,TNF-α,IL-17,and IL-18 levels,myocardial acely-FOXO1/FOXO1 were decreased(P＜0.05),the cardiac function indexes the left ventricular ejection fraction(LVEF)and the left ventricular fractional shortening(LVFS),and the expression of SIRT1 in myocardial tissue were increased(P＜0.05);the pathological injuries in myocardial tissue of the EX527 group were aggravated,the serum CK-MB,cTnⅠ,cTnT,TNF-α,IL-17,and IL-18 levels,myocardial acely-FOXO1/FOXO1 were increased(P＜0.05),the cardiac function indexes LVEF and LVFS,and the expression of SIRT1 in myocardial tissue were decreased(P＜0.05).miR-409-3p was able to target down-regulation of SIRT1 expression in rat cardiomyocytes.The study suggests that miR-409-3p can target down-regulate SIRT1 expression to participate in the process of myocardial injury in KD young rats.Down-regulation of miR-409-3p expression can play an anti-inflammatory effect by activating SIRT1/FOXO1 signal,thereby reducing myocardial injury in KD young rats.
关键词
微小RNA-409-3p/沉默信息调节因子1/叉头转录因子O1/川崎病/幼鼠/心肌损伤Key words
microRNA-409-3p/silent information regulator 1/forkhead transcription factor O1/Kawasaki disease/young rat/myocardial injury引用本文复制引用
出版年
2024
NETL
NSTL
万方数据