目的 研究miR-223调控Nod样受体蛋白3(Nod-like receptor protein 3,NLRP3)抑制心力衰竭(heart failure,HF)大鼠心肌纤维化的机制.方法 选取54只成年Wistar大鼠,采用腹主动脉缩窄法建立大鼠充血性HF动物模型,按照随机数字表法将其分为对照组、HF组、HF+miR-223过表达组,每组各18只.HF+miR-223过表达组尾静脉注射miR-223mimics,72h转染成功后,应用动物心脏彩超检测各组大鼠心功能相关指标,即舒张末期室间隔厚度(interventricular septal thickness at end-diastole,IVSd)、舒张末期左心室后壁厚度(left ventricular posterior wall thickness at end-diastolic,LVPWd)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDd)、左心室收缩末期内径(left ventricular end systolic diameter,LVED)和射血分数(left ventricular ejectfraction,LVEF).计算测定心/体比、肺/体比;检测各组大鼠心肌组织中miR-223、NL-RP3、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、Collagen-3、Collagen-1、Bax和Bcl-2的表达情况.结果 HF组心功能较对照组更差,NLRP3、IL-1β、TNF-α、Collagen-1、Collagen-3和Bax表达高于对照组,miR-223、Bcl-2表达低于对照组(P＜0.05),心肌间质纤维化程度明显加重.HF+miR-223过表达组心功能较HF组好转,NLRP3、IL-1β、TNF-α、Collagen-1、Collagen-3、Bax 表达低于 HF 组,miR-223、Bcl-2 表达高于 HF 组,心肌间质纤维化程度明显减轻.结论 miR-223可通过作用于其靶标NLRP3抑制Collagen-1、Collagen-3的表达,在HE心肌纤维化的发生、发展过程中起到重要作用.
Mechanism of MiR-223 Regulating NLRP3 to Inhibit Myocardial Fibrosis in Rats with Heart Failure
Objective To investigate the mechanism of miR-223 regulation of Nod-like receptor protein 3(NLRP3)on myocar-dial fibrosis in rats with heart failure(HE).Methods A total of fifty-four adult Wistar rats were selected to establish rat model of con-gestive HF by abdominal aortic coarctation method,and they were divided into control group,HF group,and HF+miR-223 overexpres-sion according to random number table method,with 18 rats in each group.MiR-223mimics was injected into the tail vein of HF+miR-223 overexpression group,after transfection was successful for 72h,cardiac function related indexes of rats in each group were de-tected by animal heart color ultrasound:interventricular septal thickness at end-diastole(IVSd),left ventricular posterior wall thickness at end-diastolic(LVPWd),left ventricular end-diastolic diameter(LVEDd),left ventricular end systolic diameter(LVED)and left ventricular ejectfraction(LVEF).The heart/body ratio,lung/body ratio,liver/body ratio were calculated and measured;the expression levels of miRNA-223,NLRP3,interleukin-1β(IL-1 β),tumor necrosis factor-α(TNF-α),Collagen-3,Collagen-1,Bax,and Bcl-2 in myocardial tissue of rats in each group.Results The cardiac function of the HE group was worse than that of the control group,and the expressions of NLRP3,IL-1β,TNF-α,Collagen-1,Collagen-3 and Bax were higher than those of the control group,while the expressions of miR-223 and Bcl-2 were lower than those of the control group(P＜0.05),and the degree of myocardi-al interstitial fibrosis was significantly aggravated.The cardiac function of HF+miR-223 overexpression group was better than that of the HE group,the expressions of NLRP3,IL-1 β,TNF-α,Collagen-1,Collagen-3 and Bax were lower than those of the HE group,the expressions of miR-223 and Bcl-2 were higher than those of the HE group,and the degree of myocardial interstitial fibrosis was signifi-cantly alleviated.Conclusion MiR-223 can inhibit the expression of Collagen-1 and Collagen-3 by acting on its target NLRP3,and play an important role in the occurrence and development of myocardial fibrosis in HE.
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