基于PSMs新靶点的黄连素在CA-MRSA致病中的抗炎作用与免疫机制研究

近年来，一种具有强致病力特点的社区获得性耐甲氧西林金黄色葡萄球菌（CA-MRSA）的感染日益严重，呈流行或暴发流行的趋势，治疗困难且病死率高，严重威胁人类的健康，给临床治疗带来巨大挑战。大量研究表明，酚溶调制肽（PSMs）是导致CA-MRSA强致病性的主要毒力因子。PSMs可诱导单核/巨噬细胞释放大量的炎性细胞因子，募集并激活中性粒细胞，抑制中性粒细胞的自发性凋亡，加重炎症损伤，赋予CA-MRSA强大的致病力。因此，PSMs有望成为控制和治疗CA-MRSA感染的新药物靶点。本课题组前期研究发现，黄连素可能干扰或阻断PSMs发挥生物学功能。本研究中拟明确黄连素与CA-MRSA分泌的PSMs多肽的相互作用关系，深入探讨黄连素对PSMs触发的固有免疫应答的调控作用及免疫机制，并进一步确证黄连素在CA-MRSA导致炎症损伤中的抗炎作用，为临床治疗CA-MRSA感染提供新的思路和有效途径。

In recent years, there has been an alarming epidemic caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) associated with high morbidity and mortality, which is a serious threat to human health and a great challenge for clinical treatment. Many studies have shown that phenol-soluble modulins (PSMs) are the major virulence factors that account for the high pathogenicity of CA-MRSA. PSMs can induce the production of proinflammatory cytokines in mononuclear macrophage, recruit and activate neutrophils, inhibit spontaneous apoptosis of neutrophils, and enhance inflammatory injury, which contributes to the enhanced virulence of CA-MRSA. Therefore, PSMs are expected to be novel drug targets for the control and treatment of CA-MRSA infection. Our previous studies have shown that berberine might interfere and block the biological function of PSMs. In this study, we will elucidate the interaction between berberine and PSMs polypeptides secreted by CA-MRSA, further investigate the role of berberine in PSMs triggered innate immune response, and confirm the anti-inflammatory action of berberine in CA-MRSA caused inflammatory injury, so as to provide a new thought and effect approach for the clinical treatment of CA-MRSA infection.