中药五谷虫抗MRSA感染的血清药理学及抗菌和逆转耐药机制研究

The special antibacterial effects of Chinese medicine WuGuChong (commonly known as maggots) for serious bacterial infection(such as MRSA) is on the rise on the account of its efficacy, safety and simplicity. The academic interest, however, is focused on the biological treatment and antibacterial effect in vitro at present. Our team is Asia's first research team to study WuGuChong antibacterial and biological treatment, with a lot of preliminary work based on originality. In previous study, we discovered WuGuChong can destroy the ultrastructure of bactera and promote infected wound healing. The present study under the guideline of the concept of Chinese medicine theory, will be carried out as follows: 1) to achieve animal serum contained anti-MRSA components from WuGuChong, innovate chromatography purification technology with the theory of cooperation and overall compatibility, extract serum containing the effective anti-MRSA component successfully, and obtain the key biological information to discover new anti-MRSA efficiency and compatibility of materials;2) to establish anti-MRSA model of serum containing drug of WuGuChong and to explain the ant-MRSA mechanism of WuGuChong effective components from serum in the aspects of MRSA ultra-structure, bacterial metabolism, exotoxin and bacterial biofilms.3) to clear the reverse resistance mechanisms of WuGuChong effective components from serum against MRSA in gene and protein level. The present study is to provide new methods for the effective treatment of MRSA infections in vivo, to open up innovative ideas of Chinese traditional animal medicine, and to lay the theoretical foundation for clinical translation of the "new Chinese anti-bacterial agents".

中药五谷虫（蛆虫）对严重细菌感染的特效抗菌作用日益受到国际医学界重视。本课题组作为亚洲率先进行五谷虫抗菌与生物治疗研究团队，前期工作发现五谷虫体外具有破坏耐药金葡菌超微结构和促进感染创面愈合作用（Int J Mol Med，2013）。本课题在此基础上，以中医整体观理论为指导，首创性进行如下研究：1）获取含五谷虫药物成分的动物血清，采用组分配伍整体理论对层析提纯技术进行创新，提取含药血清中的有效抗MRSA感染组分，获得生物信息，发现新的抗MRSA和配伍增效物质；2）建立含药血清抗菌模型，从MRSA超微结构、细菌代谢、外毒素及细菌生物膜等方面阐释五谷虫含药血清有效组分抗MRSA作用的特点与机理；3）从基因和蛋白水平明确MRSA在经过五谷虫含药血清有效组分作用后，其耐药特性的改变。本课题将为五谷虫抗耐药菌感染研究提供新方法，为中药动物药研究开辟新思路，为“新型中药抗菌剂”临床转化奠定理论基础。

中药五谷虫对严重细菌感染的特效抗菌作用日益受到国际医学界重视。目前研究主要集中在五谷虫抗菌物质提纯技术研究及提取物与细菌共培养后进行的体外抗菌实验研究，尚缺乏对五谷虫的体内抗菌作用和相关机理进行的基础研究。本研究以中西医结合理论为指导，以五谷虫含药血清为研究对象，首创性地研究中药五谷虫抗耐甲氧西林金黄色葡萄球菌的血清药理学，并对有效组分进行分离提纯，成功提取五谷虫含药血清中的抗耐甲氧西林金黄色葡萄球菌组分，并全面阐释中药五谷虫的体内抗耐甲氧西林金黄色葡萄球菌感染机制和和逆转耐甲氧西林金黄色葡萄球菌耐药的机理。研究结果发现，中药五谷虫含药血清有效组分有明显的抑制耐甲氧西林金黄色葡萄球菌生长作用，其机制是多方面的，包括：（1）直接破坏耐甲氧西林金黄色葡萄球菌细胞壁，在细胞壁上形成孔洞，增加细胞膜通透性，而发挥抗菌作用；（2）通过抑制耐甲氧西林金黄色葡萄球菌 α-溶血素基因和蛋白的表达，抑制耐甲氧西林金黄色葡萄球菌溶血素的生成，降低耐甲氧西林金黄色葡萄球菌的毒性；（3）直接抑制耐甲氧西林金黄色葡萄球菌与纤维蛋白原和CK10的粘附作用；（4）抑制耐甲氧西林金黄色葡萄球菌生物膜的形成。（5）通过抑制耐甲氧西林金黄色葡萄球菌耐药基因mecA mRNA 的表达，逆转耐甲氧西林金黄色葡萄球菌的耐药作用。（5）通过抑制耐甲氧西林金黄色葡萄球菌耐药蛋白PBP-2α的表达，逆转耐甲氧西林金黄色葡萄球菌的耐药作用。从而增加抗生素的敏感性。本研究明确了中药五谷虫抗耐甲氧西林金黄色葡萄球菌的作用机制及其逆转耐甲氧西林金黄色葡萄球菌的耐药机理，为中药五谷虫抗耐药菌感染研究和中药动物药研究提供新思路，为五谷虫抗菌治疗理念和技术推广与应用提供科学依据，为我国自主知识产权的“新型中药五谷虫抗菌剂”药物临床转化奠定理论基础。