韩士超, 赵欢, 徐永强, 李珍珍, 胡大海. 视黄酸相关孤核受体α对脓毒症小鼠心肌损伤的影响[J]. 心脏杂志, 2019, 31(3): 249-253. DOI: 10.12125/j.chj.201902030
    引用本文: 韩士超, 赵欢, 徐永强, 李珍珍, 胡大海. 视黄酸相关孤核受体α对脓毒症小鼠心肌损伤的影响[J]. 心脏杂志, 2019, 31(3): 249-253. DOI: 10.12125/j.chj.201902030
    Shi-chao HAN, Huan ZHAO, Yong-qiang XU, Zhen-zhen LI, Da-hai HU. Role of retinoic acid-associated orphan nuclear receptor alpha in myocardial injury in septic mice[J]. Chinese Heart Journal, 2019, 31(3): 249-253. DOI: 10.12125/j.chj.201902030
    Citation: Shi-chao HAN, Huan ZHAO, Yong-qiang XU, Zhen-zhen LI, Da-hai HU. Role of retinoic acid-associated orphan nuclear receptor alpha in myocardial injury in septic mice[J]. Chinese Heart Journal, 2019, 31(3): 249-253. DOI: 10.12125/j.chj.201902030

    视黄酸相关孤核受体α对脓毒症小鼠心肌损伤的影响

    Role of retinoic acid-associated orphan nuclear receptor alpha in myocardial injury in septic mice

    • 摘要:
        目的  本研究旨在探索视黄酸相关孤核受体α(RORα)对脓毒症炎症反应及其所致的心脏功能损害影响。
        方法  通过腹腔注射脂多糖(LPS)建立小鼠脓毒症模型,通过LPS刺激巨噬细胞,建立脓毒症细胞模型,采用细胞转染和小鼠尾静脉注射过表达质粒,以在细胞和组织中过表达RORα,进而探究RORα在脓毒症炎症反应和脓毒症所致心肌损伤中的作用。采用实时定量PCR试验、蛋白免疫印记试验检测RORα、NF-κB p65和炎症因子的变化,采用酶联免疫试验、病理切片等检测脓毒症小鼠心肌损伤的变化。
        结果  RORα在LPS刺激巨噬细胞中显著降低(P<0.05);过表达RORα能够显著抑制LPS刺激巨噬细胞中炎症因子白介素(IL)-1β和肿瘤坏死因子 (TNF)-α的表达(P<0.05)、NF-κB p65的核移位水平(P<0.05)、脓毒症小鼠血清中炎症因子IL-1β和TNF-α的释放、降低脓毒症小鼠肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)的含量以及改善脓毒症所致的心肌病理损害。
        结论  RORα能够通过抑制NF-κB p65的核移位进而负性调控LPS刺激巨噬细胞中的炎症反应,从而缓解脓毒症小鼠的炎症反应及心肌损害。

       

      Abstract:
        AIM  To investigate the role of retinoic acid-related orphan nuclear receptor alpha (RORα) in inflammatory responses and cardiac function injury to sepsis.
        METHODS  A mouse model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). Macrophage was stimulated by LPS to establish a septic cell model. Cell transfection and mouse tail vein injections of over-expression plasmids were used to over-express RORα in cells and tissues and to explore the role of RORα in inflammatory responses and myocardial damage mediated by sepsis. The changes of RORα, NF-κB p65 and inflammatory cytokines were detected by real-time quantitative PCR and Western blot. The changes of cardiac function in mice with sepsis were detected by enzyme-linked immunosorbent assay and pathological section
        RESULTS  RORα significantly decreased in LPS-stimulated macrophages (P < 0.05). Over-expression of RORα significantly inhibited the expression of inflammatory cytokines IL-1β and TNF-α in LPS-stimulated macrophages (P < 0.05). Over-expression of RORα significantly inhibited LPS stimulated nuclear translocation of NF-κB p65 in macrophages (P < 0.05). Over-expression of RORα in vivo significantly inhibited the release of inflammatory factors IL-1β and TNF-α in the serum of septic mice, reduced the content of myocardial enzymes LDH and CK-MB in septic mice and improved myocardial pathological damage mediated by sepsis.
        CONCLUSION  RORα can inhibit the inflammatory response of macrophages by inhibiting the nuclear translocation of NF-κB p65, thereby alleviating the inflammatory response and myocardial injury in mice with sepsis.

       

    /

    返回文章
    返回