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

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,1μg/kg)组、 miR-409-3p antagomir+EX527(1μg/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。

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.