香豆素衍生物介导的光动力抗耐药菌效果  

Effects of Photodynamic Therapy Mediated by Coumarin Derivative Against Drug-Resistant Bacteria

作　　者：秦洪双 陈书晗 韩旭炜 郭艳祥 闵薷楠 刘涛[3] 赵传奇[2] QIN Hong-Shuang;CHEN Shu-Han;HAN Xu-Wei;GUO Yan-Xiang;MIN Ru-Nan;LIU Tao;ZHAO Chuan-Qi(Department of Biological and Food Engineering,Lyuliang University,Lvliang 033001,China;Laboratory of Chemical Biology,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;Department of Chemical and Materials Engineering,Lyuliang University,Lvliang 033001,China;School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan 030006,China)

机构地区：[1]吕梁学院生物与食品工程系,吕梁033001 [2]中国科学院长春应用化学研究所,化学生物学实验室,长春130022 [3]吕梁学院化工与材料工程系,吕梁033001 [4]山西大学化学与化工学院,太原030006

出　　处：《应用化学》2024年第11期1639-1647,共9页Chinese Journal of Applied Chemistry

基　　金：国家自然科学基金(Nos.22122704,22377120);吉林省科技发展计划(No.20210101130JC);山西省基础研究计划(Nos.202303021211336,202203021221228);山西省研究生教育教学改革课题(No.2022YJJG302);吕梁市重点研发计划(Nos.2022SHFZ39,2023GXYF04)资助。

摘　　要：蓝光(Blue light,BL)介导的光动力疗法(PDT)不仅能有效杀死耐药细菌,还能减少对深层组织的损伤,为耐药细菌感染的治疗提供了契机。但是,用于光动力杀菌治疗的蓝光光敏剂十分有限,亟需大力开发新型蓝光光敏剂来抵抗日益严重的细菌耐药问题。香豆素类化合物具备抗炎、抗菌和抗癌等多种生物学活性,同时具有良好的光敏性和稳定性。本文研究了香豆素衍生物CDOCA作为蓝光光敏剂对耐甲氧西林金黄色葡萄球菌(MRSA)的光动力杀菌作用。结果表明,32μg/mL CDOCA在蓝光(445 nm,0.5 W/cm^(2))照射5 min后可以完全抑制浮游细菌活力。而且,48μg/mL CDOCA联合蓝光(0.5 W/cm^(2),6 min)能够彻底清除生物膜中的MRSA,同时降解生物膜。更重要的是,CDOCA(1 mg/kg)和BL(0.5 W/cm^(2),6 min)联合处理8 d可有效清除小鼠皮肤伤口上的生物膜,降低炎症反应,促进伤口愈合。本研究提供的CDOCA介导的光动力学治疗方法有望用于抗药细菌的感染治疗。Blue light(BL)mediated photodynamic therapy(PDT)can not only effectively kill drug-resistant bacteria,but also reduce the damage to deep tissues,providing a new opportunity for the treatment of drug-resistant bacterial infections.However,the blue light photosensitizers used in PDT against bacteria are very limited,and it is urgent to develop new blue light photosensitizers to overcome the growing problem of drug resistance of bacteria.Coumarin derivatives exhibit many biological activities,such as anti-inflammatory,antibiosis and anti-tumor,as well as good photosensitivity and stability.Herein,the bactericidal effects of coumarin derivative CDOCA-mediated PDT against methicillin-resistant Staphylococcus aureus(MRSA)were studied.The results showed that 32μg/mL CDOCA irradiated with blue light(445 nm,0.5 W/cm^(2))for 5 min could completely inhibit the vitality of planktic bacteria.Moreover,CDOCA(48μg/mL)combined with blue light(0.5 W/cm^(2),6 min)could fully eliminate MRSA wrapped in biofilm and degrade biofilm.More importantly,the combined treatment of CDOCA(1 mg/kg)and BL(0.5 W/cm^(2),6 min)for 8 days effectively eradicated the biofilm on the skin wounds of mice,reduced inflammation and promoted wound healing.CDOCA-mediated PDT provided in this study is expected to be used in the treatments of drug-resistant bacterial infections.

关 键 词：耐药细菌 光动力疗法 香豆素衍生物 生物膜 蓝光 

分 类 号：O643.1[理学—物理化学]