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体内研究表明,类防御素 A 和修饰型防御素 B 具有协同的抗菌和抗炎活性。

Synergistic antibacterial and anti-inflammatory activity of temporin A and modified temporin B in vivo.

机构信息

Department of Soil, Plant, Environment and Animal Production Sciences, University of Naples Federico II, School of Biotechnological Sciences, Napoli, Italy.

出版信息

PLoS One. 2009 Sep 28;4(9):e7191. doi: 10.1371/journal.pone.0007191.

Abstract

Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria). They are 10-14 amino acid long polypeptides active prevalently against gram positive bacteria. This study shows that a synthetic temporin B analogue (TB-YK), acquires the capacity to act in synergism with temporin A and to exert antimicrobial and anti-inflammatory activity in vivo against gram positive and gram negative bacteria. Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals. More importantly, the same doses of temporins, administered one week after experimental infection with a sub lethal dose of bacteria, sterilized 100% of the animals within 3-6 days. Also, it is described an animal model based on the use of sub lethal doses of bacteria, which closely mimics bacterial infection in humans. The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.

摘要

瞬态蛋白是由欧洲红蛙(Rana temporaria)颗粒腺分泌的抗菌肽。它们是 10-14 个氨基酸长的多肽,主要针对革兰氏阳性菌发挥活性。本研究表明,一种合成的瞬态蛋白 B 类似物(TB-YK)获得了与瞬态蛋白 A 协同作用的能力,并在体内对革兰氏阳性和革兰氏阴性菌具有抗菌和抗炎活性。在给与致死剂量细菌(革兰氏阳性或阴性)的个体小鼠同时给予 3.4mg/Kg 的瞬态蛋白 A(TA)+1.6mg/Kg 的 TB-YK 时,100%的动物得到挽救。更重要的是,相同剂量的瞬态蛋白在实验性感染亚致死剂量细菌后一周给予,在 3-6 天内 100%的动物被灭菌。还描述了一种基于使用亚致死剂量细菌的动物模型,该模型非常类似于人类的细菌感染。该模型提供了在临床前环境中测试 TA 和 TB-YK 联合作为抗菌和抗炎剂的真正潜力的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/2747021/bdd07904c7f7/pone.0007191.g001.jpg

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