盐酸小檗碱与左氧氟沙星联合抑制MRSA及其机制研究

养殖场抗生素滥用造成多种耐药性细菌的产生，从奶肉类制品中分离出耐甲氧西林金黄色葡萄球菌（MRSA）的案例逐年增长，对养殖业食品安全造成巨大威胁。本研究筛选出与左氧氟沙星具有联合抑制MRSA效果的天然产物盐酸小檗碱（BBR），探究BBR与其对MRSA的协同抑菌效果和联合抑菌机制。结果表明，BBR能有效抑制MRSA生长，提高MRSA对左氧氟沙星的敏感度，两者联用后，MRSA对左氧氟沙星的MIC降为之前的1/16。协同作用机制主要为上调ribA及下调mec A和msc L表达水平，破坏细胞壁、增加细胞膜的通透性，从而达到协同抑菌的目的。本研究有助于降低畜牧养殖中抗生素的使用，为提高肉奶类食品安全奠定基础。

The Inhibition and Mechanism of the Combination of Berberine Hydrochloride and Levofloxacin on MRSA

The misuse of antibiotics on farms has caused the emergence of a variety of drug-resistant bacteria. MRSA isolated from dairy meat products are increasing year by year, leading to a great threat to food safety in the farming industry. In this paper, berberine hydrochloride (BBR), a natural product with combined inhibition effect of MRSA with levofloxacin, was screened, and the synergistic inhibition effect and combined inhibition mechanism of BBR with its effect on MRSA were investigated. The results showed that BBR could effectively inhibit the growth of MRSA and improve the sensitivity of MRSA to levofloxacin, and the combination could reduce the MIC of the latter up to 1/16. The synergistic mechanism of combination was mainly up-regulation of ribA and down-regulation of mec A and msc L expression levels, disrupting the cell wall and increasing the permeability of the cell membrane, thus achieving synergistic bacterial inhibition. This thesis helps to lay the foundation for reducing the use of antibiotics in livestock farming and improving the food safety of meat and milk.