Fang Ya-Qun, Shen Chuan-Bin, Luan Ning, Yao Hui-Min, Long Chen-Bo, Lai Ren, Yan Xiu-Wen
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; University of Chinese Academy of Sciences, Beijing 100009, China.
Chin J Nat Med. 2017 Mar;15(3):161-167. doi: 10.1016/S1875-5364(17)30032-8.
The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1β, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF-α, and IFN-γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity.
本研究旨在探讨合成的铁调素的抗疟活性及其对感染伯氏疟原虫小鼠细胞因子分泌的影响。小鼠经静脉感染伯氏疟原虫,并根据4天抑制试验和拉内试验用铁调素进行治疗。使用细胞计数珠阵列(CBA)试剂盒测定实验小鼠血清中白细胞介素(IL-1β、IL-2、IL-6、IL-10、IL-12p70和IL-17A)、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的水平。还记录了感染小鼠的存活率。此外,检测血清铁、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和总胆红素(BIL)以评估肝功能。铁调素在体内发挥直接抗疟作用,并以剂量依赖方式提高存活率。此外,铁调素抑制1型辅助性T细胞(Th1)、Th2和Th17细胞因子、TNF-α和IFN-γ的分泌。总之,我们的结果表明,合成的铁调素在体内具有抗疟活性并具有抗炎功能,这为未来设计具有理想抗疟活性的新衍生物提供了依据。