Sepsis is a whole-body inflammation and main cause of death in intensive care units worldwide. We aimed to investigate the roles of lncRNA MIAT and miR-330-5p in modulating inflammatory responses and oxidative stress in lipopolysachariden (LPS)-induced septic cardiomyopathy. Serum and heart tissue were collected from in vivo septic mice model, ELISA and qRT-PCR were used to measure the expression of pro-inflammation cytokines, MIAT and miR-330-5p, respectively. The knockdown of MIAT and overexpression of miR-330-5p were conducted to assess their effects on regulating inflammation response and intracellular oxidative stress in LPS-stimulated HL-1 cells. The reactive oxygen (ROS) level, mitochondrial membrane potential (MMP), GSH/GSSH ratio, and lipid peroxidation assessment (MDA) were used to evaluate the intracellular oxidative stress. Dual-luciferase reporter assay was performed to identify the association between MIAT and miR-330-5p, TRAF6 and miR-330-5p, respectively. In septic mice, the expression of MIAT and pro-inflammation cytokines was elevated while the expression of miR-330-5p decreased. Knockdown of MIAT or overexpression of miR-330-5p restrained inflammation and oxidative stress induced by LPS in vitro; MIAT directly targeted miR-330-5p to regulate NF-κB signaling, and miR-330-5p targeted against TRAF6 to suppress the activation of NF-κB signaling. We determined that lncRNA MIAT directly binds to miR-330-5p to activate TRAF6/NF-κB signaling axis and further promotes inflammation response as well as oxidative stress in LPS-induced septic cardiomyopathy. This finding suggests the potential therapeutic role of lncRNA MIAT and miR-330-5p in LPS-induced myocardial injury.

脓毒症是全身炎症，是全球重症监护病房的主要死亡原因。我们旨在研究lncRNA MIAT和miR-330-5p在调节脂多糖（LPS）诱导的败血症性心肌病的炎症反应和氧化应激中的作用。从体内脓毒症小鼠模型中收集血清和心脏组织，ELISA和qRT-PCR分别测量促炎细胞因子MIAT和miR-330-5p的表达。进行了MIAT抑制和miR-330-5p的过表达，以评估它们对LPS刺激的HL-1细胞中炎症反应和细胞内氧化应激的调节作用。使用活性氧（ROS）水平，线粒体膜电位（MMP），GSH / GSSH比和脂质过氧化评估（MDA）来评估细胞内的氧化应激。进行双荧光素酶报告基因测定以分别鉴定MIAT与miR-330-5p，TRAF6和miR-330-5p之间的关联。在脓毒症小鼠中，MIAT和促炎细胞因子的表达升高，而miR-330-5p的表达降低。MIAT的抑制或miR-330-5p的过表达抑制了LPS体外诱导的炎症和氧化应激；MIAT直接靶向miR-330-5p来调节NF-κB信号，而miR-330-5p靶向TRAF6来抑制NF-κB信号的激活。我们确定lncRNA MIAT直接与miR-330-5p结合以激活TRAF6 /NF-κB信号转导轴，并进一步促进LPS诱导的败血性心肌病的炎症反应以及氧化应激。这一发现表明lncRNA MIAT和miR-330-5p在LPS诱导的心肌损伤中的潜在治疗作用。