抗菌肽(AMPs)代表了一种有前途的抗生素替代品,通过插入细菌膜来克服耐药细菌,导致细胞裂解。然而,AMPs的治疗应用受到其裂解真核细胞的能力的阻碍。GF-17是LL-37的截短肽,具有完美的两亲性和较高的疏水性,导致更高的溶血活性。然而,GF-17和LL-37组对人肺上皮细胞的细胞毒性没有显着差异,表明不同人体细胞对GF-17的敏感性存在显著差异。在这项研究中,通过鼻内接种对小鼠肺施用LL-37和GF-17。血常规检查结果显示LL-37对红细胞无影响,血小板,白细胞和中性粒细胞计数,但随着肽浓度的增加,GF-17降低了白细胞和中性粒细胞的数量。GF-17处理的小鼠在24小时内平均体重减轻约2.3g,这表明GF-17对小鼠具有高毒性。GF-17处理小鼠的支气管肺泡灌洗液中的总细胞计数是未处理组的4.66倍,这表明GF-17治疗导致小鼠肺部炎症。同样,组织学结果显示GF-17处理的小鼠肺中嗜中性粒细胞浸润。结果表明,在小鼠肺部施用GF-17不会影响血液中的红细胞和血小板计数,但会促进肺部中性粒细胞浸润,导致炎症反应。因此,建立小鼠急性肺损伤模型,初步评价AMPs的体内毒性。对于具有临床应用价值的AMP,仍需要系统的研究来评估其急性和长期毒性。
Antimicrobial peptides (AMPs) represent a promising antibiotic alternative to overcome drug-resistant bacteria by inserting into the membrane of bacteria, resulting in cell lysis. However, therapeutic applications of AMPs have been hindered by their ability to lyse eukaryotic cells. GF-17 is a truncated peptide of LL-37, which has perfect amphipathicity and a higher hydrophobicity, resulting in higher haemolytic activity. However, there is no significant difference in the cytotoxicity against human lung epithelial cells between the GF-17 and LL-37 groups, indicating that there are significant differences in the sensitivity of different human cells to GF-17. In this study, LL-37 and GF-17 were administered to mouse lungs via intranasal inoculation. Blood routine examination results showed that LL-37 did not affect the red blood cells, platelet, white blood cells and neutrophil counts, but GF-17 decreased the white blood cells and neutrophil counts with the increasing concentration of peptides. GF-17-treated mice suffer a body weight loss of about 2.3 g on average in 24 h, indicating that GF-17 is highly toxic to mice. The total cell counts in the bronchoalveolar lavage fluid from GF-17-treated mice were 4.66-fold that in the untreated group, suggesting that GF-17 treatment leads to inflammation in the lungs of mice. Similarly, the histological results showed the infiltration of neutrophils in the lungs of GF-17-treated mice. The results suggest that the administration of GF-17 in the lungs of mice does not affect the red blood cells and platelet counts in the blood but promotes neutrophil infiltration in the lungs, leading to an inflammatory response. Therefore, we established a mouse acute lung injury model to preliminarily evaluate the in vivo toxicity of AMPs. For AMPs with a clinical application value, systematic research is still needed to evaluate their acute and long-term toxicity.