首页|下调miR-223表达对脓毒症心肌病小鼠心肌的保护作用及机制研究

下调miR-223表达对脓毒症心肌病小鼠心肌的保护作用及机制研究

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目的:探讨下调miR-223表达对脓毒症心肌病(SCM)小鼠心肌的保护作用及其机制。方法:按随机数字表法将27只8-10周龄 SPF 级雄性 C57BL/6 小鼠分配至 SCM 模型(0 h,6 h,12 h,18 h,24 h)时相组、Normal 组、SCM 组、miR-223 antagomir NC 组、miR-223 antagomir 组,每组 3 只。腹腔注射脂多糖(lipopolysaccharide,LPS)15 mg/kg 构建 SCM 小鼠模型。miR-223 antagomir NC组与miR-223 antagomir组分别于建模前连续3天鼠尾静脉注射miR-223 antagomir NC、miR-223 antagomir预处理。采用反转录-聚合酶链反应(RT-PCR)研究SCM模型各个时相组小鼠心肌组织miR-223的表达情况。采用苏木素伊红(HE)染色法观察Normal组、SCM组、miR-223 antagomir NC组和miR-223 antagomir组小鼠心肌病理形态变化。采用酶联免疫吸附实验(ELISA)测定 Normal 组、SCM 组、miR-223 antagomir NC 组和 miR-223 antagomir 组小鼠血清 cTnⅠ、BNP、CK-MB、IL-6、IL-1β、TNF-α 的含量并进行相关性分析。结果:SCM模型时相组小鼠随刺激时间延长,心肌组织miR-223表达水平逐渐升高。与Normal组比较,SCM组、miR-223 antagomir NC组、miR-223 antagomir组小鼠心肌组织出现不同程度损伤;血清心肌损伤标记物cTnⅠ、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α的表达水平均上升,差异具有统计学意义(P<0。05);与SCM组比较,miR-223 antagomir NC组各项指标相差不大,差异均无统计学意义(P>0。05);miR-223 antagomir组小鼠心肌组织病理损伤程度有所减轻,心肌损伤标记物cTnⅠ、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α水平下降,差异具有统计学意义(P<0。05)。相关性分析结果显示小鼠miR-223表达与心肌损伤标记物cTnⅠ、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α的表达呈正相关。结论:下调miR-223表达可通过减轻炎症反应对SCM小鼠心肌产生保护作用。
Protective Effect and Mechanism of Down-regulation of miR-223 Expression on Myocardium of Septic Cardiomyopathy Mice
Objective:Investigating the protective effect and mechanisms of downregulating miR-223 expression on the myocardium of mice with septic cardiomyopathy(SCM).Methods:Using a random number table,27 male SPF C57BL/6 mice aged 8-10 weeks were allocated into different groups:SCM model groups at different time points(0 h,6 h,12 h,18 h,24 h),Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group,with 3 mice in each group.The SCM mouse model was established by intraperitoneal injection of lipopolysaccharide(LPS)at a dose of 15 mg/kg.The miR-223 antagomir NC group and miR-223 antagomir group received consecutive tail vein injections of miR-223 antagomir NC and miR-223 antagomir,respectively,for 3 days before modeling.Reverse transcription-polymerase chain reaction(RT-PCR)was used to study the expression of miR-223 in the myocardial tissue of mice in different time point groups of the SCM model.Hematoxylin-eosin(HE)staining was performed to observe the myocardial pathological changes in the Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of cTnⅠ,BNP,CK-MB,IL-6,IL-1β,and TNF-α in mouse serum in the Normal group,SCM group,miR-223 antagomir NC group,and miR-223 antagomir group,and correlation analysis was conducted.Results:In the SCM model groups at different time points,the expression level of miR-223 in the myocardial tissue gradually increased with the extension of stimulation time.Compared to the Normal group,mice in the SCM group,miR-223 antagomir NC group,and miR-223 antagomir group exhibited varying degrees of myocardial damage.The expression levels of cardiac injury markers cTnⅠ,BNP,CK-MB,and inflammatory factors IL-6,IL-1 β,and TNF-α in serum were elevated,and the differences were statistically significant(P<0.05).When compared to the SCM group,there were no significant differences in various indicators between the miR-223 antagomir NC group(P>0.05).In the miR-223 antagomir group,the degree of pathological damage in the myocardial tissue was reduced,and the levels of cardiac injury markers cTnⅠ,BNP,CK-MB,and inflammatory factors IL-6,IL-1β,and TNF-α decreased,with statistically significant differences(P<0.05).The results of correlation analysis showed that the expression of miR-223 in mice was positively correlated with the expression of cardiac injury markers cTnI,BNP,CK-MB,and inflammatory factors IL-6,IL-1β,and TNF-α.Conclusion:Downregulation of miR-223 expression can provide protection to the myocardium of SCM mice by alleviating the inflammatory response.

SepsisSeptic cardiomyopathymiR-223miRNAInflammatory response

董玉杰、王晓景、阮国然、任浩进、陈诗阳、黄海东、张美春

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武汉科技大学医学院 湖北武汉 430080

武汉科技大学附属普仁医院心血管内科 湖北武汉 430080

武汉科技大学附属普仁医院风湿免疫科 湖北武汉 430080

脓毒症 脓毒症心肌病 miR-223 miRNA 炎症反应

湖北省自然科学基金面上项目武汉市医学科研项目

2019CFB621WX20Q27

2024

现代生物医学进展
黑龙江省森工总医院 哈尔滨医科大学附属第四医院

现代生物医学进展

CSTPCD
影响因子:0.755
ISSN:1673-6273
年,卷(期):2024.24(2)
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