Baicalein Inhibits HMGB1 Release and MMP-2/-9 Expression in Lipopolysaccharide-Induced Cardiac Hypertrophy
Baicalein Inhibits HMGB1 Release and MMP-2/-9 Expression in Lipopolysaccharide-Induced Cardiac Hypertrophy
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DOI：
10.1142/s0192415x14500505
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发表时间：
2014-01-01
影响因子：
5.7
通讯作者：
Yeh, Jwu-Lai
中科院分区：
文献类型：
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作者：
Chen, Huai-Min;Liou, Shu-Fen;Yeh, Jwu-Lai
心肌功能障碍是脓毒症后常见的并发症，是脓毒症休克患者死亡的重要原因。在寻找潜在的有效药物，以减少死亡率从败血症，我们研究了黄芩素，黄酮类化合物存在于黄芩的根，对脂多糖（LPS）诱导的促炎细胞因子的产生和基质金属蛋白酶-2和-9（MMP-2/-9）的表达的心脏保护作用。我们发现，黄芩素显着衰减LPS诱导的心肌肥大和抵消活性氧（ROS）的产生在新生大鼠心肌细胞。此外，黄芩素预处理可抑制LPS诱导的早期（e.例如，在一个实施例中，肿瘤坏死因子-α（TNF-α）和白细胞介素-6）和晚期（例如，高迁移率族蛋白1（HMGB 1）促炎细胞因子释放、诱导型一氧化氮合酶（iNOS）表达和NO产生。黄芩素还能显著下调MMP-2/-9的表达，并抑制HMGB 1从细胞核向细胞质的转位。提示黄芩素可通过抑制ROS和炎性细胞因子的产生，对LPS诱导的心肌损伤具有保护作用。这些心脏保护作用可能通过抑制HMGB 1和MMP-2/-9信号通路介导。
Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e. g., tumor necrosis factor-alpha (TNF-alpha) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.