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芦荟大黄素介导的光动力疗法可减轻体外选定革兰阳性菌中与脓毒症相关的毒素。

Aloe-Emodin-Mediated Photodynamic Therapy Attenuates Sepsis-Associated Toxins in Selected Gram-Positive Bacteria In Vitro.

机构信息

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, P.R. China.

出版信息

J Microbiol Biotechnol. 2021 Sep 28;31(9):1200-1209. doi: 10.4014/jmb.2105.05024.

Abstract

Sepsis is an acute inflammatory response that leads to life-threatening complications if not quickly and adequately treated. Cytolysin, hemolysin, and pneumolysin are toxins produced by gram-positive bacteria and are responsible for resistance to antimicrobial drugs, cause virulence and lead to sepsis. This work assessed the effects of aloe-emodin (AE) and photodynamic therapy (PDT) on sepsis-associated gram-positive bacterial toxins. Standard and antibiotic-resistant , , and bacterial strains were cultured in the dark with varying AE concentrations and later irradiated with 72 J/cm light. Colony and biofilm formation was determined. CCK-8, Griess reagent reaction, and ELISA assays were done on bacteria-infected RAW264.7 cells to determine the cell viability, NO, and IL-1β and IL-6 pro-inflammatory cytokines responses, respectively. Hemolysis and western blot assays were done to determine the effect of treatment on hemolysis activity and sepsis-associated toxins expressions. AE-mediated PDT reduced bacterial survival in a dose-dependent manner with 32 μg/ml of AE almost eliminating their survival. Cell proliferation, NO, IL-1β, and IL-6 cytokines production were also significantly downregulated. Further, the hemolytic activities and expressions of cytolysin, hemolysin, and pneumolysin were significantly reduced following AE-mediated PDT. In conclusion, combined use of AE and light (435 ± 10 nm) inactivates MRSA, (ATCC 29213), (ATCC 49619), MDR-, (ATCC 29212), and VRE (ATCC 51299) in an AE-dose dependent manner. AE and light are also effective in reducing biofilm formations, suppressing pro-inflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.

摘要

脓毒症是一种急性炎症反应,如果不能迅速和充分地治疗,可能会导致危及生命的并发症。细胞溶解素、溶血素和肺炎球菌溶血素是革兰氏阳性菌产生的毒素,它们对抗生素耐药,导致毒力并导致脓毒症。本研究评估了大黄素(AE)和光动力疗法(PDT)对脓毒症相关革兰氏阳性菌毒素的影响。标准和抗生素耐药的 、 、 和 细菌菌株在黑暗中用不同浓度的 AE 培养,然后用 72 J/cm 的光照射。测定菌落和生物膜形成。用 CCK-8、Griess 试剂反应和 ELISA 检测法分别在细菌感染的 RAW264.7 细胞上检测细胞活力、NO 和促炎细胞因子 IL-1β和 IL-6 的反应。进行溶血和 Western blot 测定以确定治疗对溶血活性和脓毒症相关毒素表达的影响。AE 介导的 PDT 以剂量依赖性方式降低细菌存活率,32μg/ml 的 AE 几乎消除了其存活率。细胞增殖、NO、IL-1β和 IL-6 细胞因子的产生也显著下调。此外,AE 介导的 PDT 后细胞溶解素、溶血素和肺炎球菌溶血素的溶血活性和表达也显著降低。总之,AE 和光(435±10nm)的联合使用以 AE 剂量依赖性方式使 MRSA、 (ATCC 29213)、 (ATCC 49619)、MDR-、 (ATCC 29212)和 VRE(ATCC 51299)失活。AE 和光也可有效减少生物膜形成,抑制促炎细胞因子、溶血活性,并抑制引起脓毒症的毒素表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c286/9705996/e102daca20e0/jmb-31-9-1200-f1.jpg

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