Department of Cardiology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, China.
Department of National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
ESC Heart Fail. 2023 Apr;10(2):931-942. doi: 10.1002/ehf2.14235. Epub 2022 Dec 1.
Myocardial ischaemia/reperfusion injury (MIRI) is a major cause of heart failure after myocardial infarction. Berberine (BBR) presents anti-inflammatory and immunosuppressive properties in many diseases. Our research looked into the therapeutic effects and mechanism of BBR in MIRI.
MIRI animal and cell models were established. The mRNA and protein expressions were assessed using reverse transcription and quantitative real-time polymerase chain reaction and western blot. The haemodynamic parameters (left ventricular ejection fraction and left ventricular ejection fraction) were detected by echocardiography. The myocardial infarct size and myocardium lesion were assessed by triphenyltetrazolium chloride and haematoxylin-eosin staining. The levels of injury factors were determined by ELISA. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining was performed to analyse cell apoptosis. Dual luciferase reporter gene and RNA immunoprecipitation assays were carried out to verify the interaction between miR-340-5p and HMGB1. BBR administration could improve the haemodynamic parameters and infarct size in MIRI rats (all P < 0.05). In MIRI rat model, BBR reduced cardiomyocyte apoptosis and inflammation (all P < 0.05). BBR could promote miR-340-5p expression (0.64 ± 0.21, P < 0.05), which is lowly expressed in MIRI group (0.24 ± 0.10, P < 0.01) in compare with the sham group (0.99 ± 0.01). MiR-340-5p knockdown abolished the protective effects of BBR on H/R-treated cardiomyocytes (all P < 0.05). BBR suppressed the HMGB1/TLR4/NF-κB pathway activation in MIRI. HMGB1 functioned as the target of miR-340-5p, and its silencing reversed the effect of miR-340-5p inhibitor on BBR-treated MIRI.
In MIRI, BBR repressed HMGB1-mediated TLR4/NF-κB signalling pathway through miR-340-5p to suppress cardiomyocyte apoptosis and inflammation.
心肌缺血/再灌注损伤（MIRI）是心肌梗死后心力衰竭的主要原因。小檗碱（BBR）在许多疾病中具有抗炎和免疫抑制作用。我们的研究探讨了 BBR 在 MIRI 中的治疗作用和机制。
建立了 MIRI 动物和细胞模型。使用逆转录和实时定量聚合酶链反应和 Western blot 评估 mRNA 和蛋白质表达。通过超声心动图检测血流动力学参数（左心室射血分数和左心室射血分数）。通过氯化三苯基四氮唑和苏木精-伊红染色评估心肌梗死面积和心肌损伤。通过 ELISA 测定损伤因子水平。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色分析细胞凋亡。双荧光素酶报告基因和 RNA 免疫沉淀测定验证 miR-340-5p 与 HMGB1 之间的相互作用。BBR 给药可改善 MIRI 大鼠的血流动力学参数和梗死面积（均 P<0.05）。在 MIRI 大鼠模型中，BBR 减少了心肌细胞凋亡和炎症（均 P<0.05）。BBR 可促进 miR-340-5p 表达（0.64±0.21，P<0.05），与 sham 组（0.99±0.01）相比，MIRI 组（0.24±0.10，P<0.01）中 miR-340-5p 表达水平较低。miR-340-5p 敲低消除了 BBR 对 H/R 处理的心肌细胞的保护作用（均 P<0.05）。BBR 抑制 MIRI 中 HMGB1/TLR4/NF-κB 通路的激活。HMGB1 是 miR-340-5p 的靶标，其沉默逆转了 miR-340-5p 抑制剂对 BBR 处理的 MIRI 的影响。
在 MIRI 中，BBR 通过 miR-340-5p 抑制 HMGB1 介导的 TLR4/NF-κB 信号通路抑制心肌细胞凋亡和炎症。
