Department of Pathology, Catholic University of Daegu, College of Medicine, 3056–6 Daemyung 4-Dong, Nam-Gu, Daegu 705–718, Republic of Korea.
Exp Biol Med (Maywood). 2011 Nov;236(11):1306-13. doi: 10.1258/ebm.2011.011127. Epub 2011 Oct 3.
Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. Melittin, the major bioactive component in the venom of honey bee Apis mellifera, is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and proinflammatory properties. However, the molecular mechanisms responsible for the anti-inflammatory activity of melittin have not been elucidated in liver fibrosis. We investigated whether melittin ameliorates liver inflammation and fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co-treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic stellate cells (HSCs) were cultured with tumor necrosis factor α in the absence or presence of melittin. Melittin suppresses the expression of proinflammatory cytokines through the nuclear factor (NF)-κB signaling pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken together, melittin prevents TAA-induced liver fibrosis by inhibiting liver inflammation and fibrosis, the mechanism of which is the interruption of the NF-κB signaling pathway. These results suggest that melittin could be an effective agent for preventing liver fibrosis.
肝纤维化是一种针对慢性肝损伤的愈合和瘢痕形成过程。损伤后，会发生急性炎症反应，导致中度细胞坏死和细胞外基质损伤。蜂毒肽是蜜蜂（Apis mellifera）毒液中的主要生物活性成分，是一种 26 个残基的两亲肽，具有众所周知的细胞溶解、抗菌和促炎特性。然而，蜂毒肽抗炎活性的分子机制在肝纤维化中尚未阐明。我们研究了蜂毒肽是否能改善硫代乙酰胺（TAA）诱导的肝纤维化中的肝炎症和纤维化。两组小鼠分别用 TAA（200mg/L，饮用水）处理，一组用蜂毒肽（0.1mg/kg）共同处理 12 周，另一组则不用。在缺乏或存在蜂毒肽的情况下，将肝星状细胞（HSCs）与肿瘤坏死因子 α 共培养。蜂毒肽通过核因子（NF）-κB 信号通路抑制促炎细胞因子的表达。此外，蜂毒肽在体外减少 HSCs 的活性，并降低 TAA 诱导的肝纤维化中纤维化基因反应的表达。总之，蜂毒肽通过抑制肝炎症和纤维化来预防 TAA 诱导的肝纤维化，其机制是阻断 NF-κB 信号通路。这些结果表明，蜂毒肽可能是预防肝纤维化的有效药物。
