Although inflammation plays an important role in myocardial ischemia/reperfusion injury (MI/RI), an anti-inflammatory treatment with a single target has little clinical efficacy due to the multifactorial disorders involved in MI/RI. miR-24 can achieve multitarget regulation in several diseases, suggesting that this factor may have ideal effects on alleviation of MI/RI. In present study, bioinformatics method was used to screen potential therapeutic targets of miR-24 associated with MI/RI. Three days before ischemia/reperfusion (I/R) surgery, rats in the I/R, miR-24 and adenovirus-negative control (Ad-NC) groups were injected with saline, miR-24, and Ad-NC (0.1 mL of 5 × 109 PFU/mL), respectively. Myocardial enzymes, myocardial infarct size, cardiac function, and the possible molecular mechanism were subsequently analyzed. In contrast to the level of S100A8, the level of miR-24 in myocardial tissue was significantly reduced after 30 min of ischemia followed by reperfusion for 2 h. Overexpression of miR-24 reduced the myocardial infarction area and improved the heart function of rats 3 days after MI/RI. Moreover, miR-24 inhibited infiltration of inflammatory cells in the peri-infarction area and decreased creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) release. Interestingly, miR-24 upregulation reduced S100A8 expression, followed by inhibition of TLR4/MyD-88/NF-κB signaling activation. In conclusion, miR-24 can alleviate MI/RI via inactivation of the S100A8/TLR4/MyD-88/NF-κB signaling pathway.

中文翻译：

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miR-24 通过阻断 S100A8/TLR4/MyD88/NF-κB 通路减轻 MI/RI。

尽管炎症在心肌缺血/再灌注损伤 (MI/RI) 中起重要作用，但由于 MI/RI 涉及多因素疾病，单一靶点的抗炎治疗几乎没有临床疗效。miR-24可以在多种疾病中实现多靶点调控，提示该因子可能对缓解MI/RI有理想的效果。本研究采用生物信息学方法筛选与 MI/RI 相关的 miR-24 的潜在治疗靶点。缺血/再灌注 (I/R) 手术前 3 天，I/R、miR-24 和腺病毒阴性对照 (Ad-NC) 组大鼠分别注射生理盐水、miR-24 和 Ad-NC (0.1 mL) 5 × 109 PFU/mL），分别。随后分析了心肌酶、心肌梗死面积、心脏功能和可能的分子机制。与 S100A8 的水平相比，心肌组织中 miR-24 的水平在缺血 30 分钟后再灌注 2 小时后显着降低。miR-24的过表达减少了心肌梗死面积，改善了MI/RI后3天大鼠的心功能。此外，miR-24 抑制梗死周围区域炎症细胞的浸润，并减少肌酸激酶心肌带 (CK-MB) 和乳酸脱氢酶 (LDH) 的释放。有趣的是，miR-24 上调降低了 S100A8 的表达，随后抑制了 TLR4/MyD-88/NF-κB 信号激活。总之，miR-24 可以通过 S100A8/TLR4/MyD-88/NF-κB 信号通路的失活来缓解 MI/RI。miR-24的过表达减少了心肌梗死面积，改善了MI/RI后3天大鼠的心功能。此外，miR-24 抑制梗死周围区域炎症细胞的浸润，并减少肌酸激酶心肌带 (CK-MB) 和乳酸脱氢酶 (LDH) 的释放。有趣的是，miR-24 上调降低了 S100A8 的表达，随后抑制了 TLR4/MyD-88/NF-κB 信号激活。总之，miR-24 可以通过 S100A8/TLR4/MyD-88/NF-κB 信号通路的失活来缓解 MI/RI。miR-24的过表达减少了心肌梗死面积，改善了MI/RI后3天大鼠的心功能。此外，miR-24 抑制梗死周围区域炎症细胞的浸润，并减少肌酸激酶心肌带 (CK-MB) 和乳酸脱氢酶 (LDH) 的释放。有趣的是，miR-24 上调降低了 S100A8 的表达，随后抑制了 TLR4/MyD-88/NF-κB 信号激活。总之，miR-24 可以通过 S100A8/TLR4/MyD-88/NF-κB 信号通路的失活来缓解 MI/RI。miR-24 上调降低 S100A8 表达，随后抑制 TLR4/MyD-88/NF-κB 信号激活。总之，miR-24 可以通过 S100A8/TLR4/MyD-88/NF-κB 信号通路的失活来缓解 MI/RI。miR-24 上调降低 S100A8 表达，随后抑制 TLR4/MyD-88/NF-κB 信号激活。总之，miR-24 可以通过 S100A8/TLR4/MyD-88/NF-κB 信号通路的失活来缓解 MI/RI。