Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice
Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice
复制标题
黄芩素通过抑制小鼠炎症和细胞凋亡来防止多种微生物脓毒症引起的肝损伤。
DOI：
10.1016/j.ejphar.2014.12.014
复制
发表时间：
2015-02-05
影响因子：
5
通讯作者：
Dirsch, Olaf
中科院分区：
文献类型：
--
作者：
Liu, Anding;Wang, Wenjie;Dirsch, Olaf
已知肝功能不全经常发生在脓毒症病例中。黄芩素是紫藤根的主要活性成分，在内毒素休克中发挥抗炎和抗凋亡作用。然而，黄芩素在多菌败血症诱导的肝损伤中的作用及其调控机制尚不清楚。本研究旨在观察黄芩素对脓毒症肝损伤的保护作用并探讨其可能的机制。采用盲肠结扎穿孔法（CLP）诱导C57 BL/6小鼠多菌性脓毒症。分别于CLP后1、6、12 h腹腔注射黄芩素100 mg/kg。黄芩素能显著提高脓毒症小鼠的存活率。黄芩素治疗可改善CLP诱导的肝损伤，如血清转氨酶水平降低和组织病理学异常减少所示。黄芩素可减少中性粒细胞浸润和肝脏炎性细胞因子的表达和释放。它还降低了脓毒症小鼠肝脏和血清中高迁移率族蛋白1和巨噬细胞移动抑制因子的水平。黄芩素还能显著抑制丝裂原活化蛋白激酶（MAPK）的活化和核因子-κ B（NF-κ B）的转录活性。结果提示，黄芩素对脓毒症小鼠肝损伤具有保护作用，并能提高脓毒症小鼠的生存率。黄芩素的保护作用机制似乎涉及其减少炎症反应、抑制肝细胞凋亡、抑制MAPK和NP-κ B活化的能力。(C)2014爱思唯尔有限公司版权所有。
Liver dysfunction has been known to occur frequently in cases of sepsis. Baicalein, the main active ingredient of the Scutellaria root, exerts anti-inflammatory and anti-apoptotic properties in endotoxic shock. However, the role of baicalein in polymicrobial sepsis-induced liver injury and its regulatory mechanisms remain unclear. In this study, we aimed to investigate the protective effects of baicalein on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were treated with baicalein (100 mg/kg, i.p) at 1 h, 6 h and 12 h following CLP. Baicalein significantly improved the survival of septic mice. Treatment with baicalein ameliorated the CLP-induced liver injury, as indicated by the lower serum aminotransferase levels and the fewer histopathologic abnormalities. Baicalein reduced the neutrophil infiltration and the hepatic inflammatory cytokine expression and release. It also decreased the hepatic and the serum high-mobility group box 1 and macrophage migration inhibitory factor levels in septic mice. Moreover, baicalein significantly inhibited the mitogen-activated protein kinases (MAPKs) activation and suppressed the transcriptional activity of nuclear factor-kappa B (NF-kappa B). In conclusion, these results suggest that baicalein treatment could protect against the sepsis-induced liver injury, and improve the survival of mice with polymicrobial sepsis. The mechanism of the protective action of baicalein seems to involve its ability to reduce inflammatory response, to inhibit hepatic apoptosis, and to suppress MAPKs and NP-kappa B activation. (C) 2014 Elsevier B.V. All rights reserved.