Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China; Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, 1 Drackendorfer straße, Jena 07747, Germany.
Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, 627 Wuluo Road, Wuhan 430070, China.
Eur J Pharmacol. 2015 Feb 5;748:45-53. doi: 10.1016/j.ejphar.2014.12.014. Epub 2014 Dec 20.
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 (100mg/kg, i.p) at 1h, 6h and 12h 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-κB). 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 NF-κB activation.
肝功能障碍在脓毒症病例中经常发生。黄芩素是黄芩根的主要活性成分，在内毒素休克中具有抗炎和抗细胞凋亡作用。然而，黄芩素在多微生物脓毒症诱导的肝损伤中的作用及其调节机制尚不清楚。在这项研究中，我们旨在研究黄芩素对多微生物脓毒症诱导的肝损伤的保护作用，并探讨其可能的机制。采用盲肠结扎穿刺术（CLP）诱导 C57BL/6 小鼠多微生物脓毒症。CLP 后 1h、6h 和 12h ，腹腔注射黄芩素（100mg/kg）治疗小鼠。黄芩素显著提高了脓毒症小鼠的存活率。黄芩素治疗改善了 CLP 诱导的肝损伤，血清转氨酶水平降低，组织病理学异常减少。黄芩素减少了中性粒细胞浸润和肝脏炎症细胞因子的表达和释放。它还降低了脓毒症小鼠的肝组织和血清高迁移率族蛋白 1 和巨噬细胞移动抑制因子水平。此外，黄芩素显著抑制丝裂原激活蛋白激酶（MAPKs）的激活，并抑制核因子-κB（NF-κB）的转录活性。总之，这些结果表明，黄芩素治疗可以防止脓毒症引起的肝损伤，并提高多微生物脓毒症小鼠的存活率。黄芩素的保护作用机制可能与其降低炎症反应、抑制肝细胞凋亡以及抑制 MAPKs 和 NF-κB 激活的能力有关。
