大蒜素调控中性粒细胞功能抗白色念珠菌感染的作用机制研究  

Allicin protects against C.albicans infection by increasing the production of ROS in neutrophils through phosphorylation of p38 MAPK

作　　者：蔡元圆 徐璐 钱峰[1] CAI Yuanyuan;XU Lu;QIAN Feng(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 201100,China)

机构地区：[1]上海交通大学药学院,上海201100

出　　处：《石河子大学学报（自然科学版）》2023年第4期480-487,共8页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(82173821,81973329)。

摘　　要：目的探究大蒜素调控中性粒细胞杀菌功能抗白色念珠菌感染的作用机制。方法建立系统性白色念珠菌感染的小鼠模型,通过组织切片染色和肾脏真菌载量检测,验证大蒜素抗白色念珠菌感染的作用;采用体外杀菌实验和超氧化物检测技术,探究大蒜素对中性粒细胞杀菌能力及ROS产生的影响;通过免疫印迹法检测p38 MAPK,JNK,ERK1/2的磷酸化水平,探究大蒜素对丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路的影响。结果大蒜素治疗显著降低了小鼠的肾脏真菌负荷;体外实验结果表明,白色念珠菌感染过程中,大蒜素增强了中性粒细胞的杀菌作用并促进了ROS的产生;此外,免疫印迹结果表明,大蒜素对中性粒细胞释放ROS的促进作用依赖于p38 MAPK的激活。结论大蒜素通过增强p38 MAPK的激活促进中性粒细胞释放ROS,从而发挥抗白色念珠菌感染的作用,可能成为治疗真菌感染的潜力化合物。Objective To investigate the antifungal activity and immunoregulatory effect of allicin during Candida albican s(C.albicans)infection.Method The mouse with systemic C.albicans infection model was used to evaluate the antifungal property of allicin.The fungal burden of kidneys was performed by PAS staining.The impact of allicin on fungicidal activity and reactive oxygen species(ROS)production of neutrophils was assessed through in vitro fungicidal assays and superoxide detection.Western blot was used to determine the activation of the MAPK pathway.Results Allicin reduced fungal loads in kidneys of C.albicans-infected mice.Moreover,allicin dose-dependently enhanced the fungicidal activity of neutrophils and promoted ROS secretion during C.albicans infection.The phosphorylation of p38 MAPK in C.albicans-infected neutrophils was enhanced by allicin,which accounted for the promotional effect of allicin on ROS production in neutrophils.Conclusion Allicin promoted ROS release from neutrophils by enhancing the activation of p38 MAPK,thereby exerting its antifungal properties and potentially serving as a promising compound for treating fungal infections.

关 键 词：大蒜素 白色念珠菌 中性粒细胞 ROS p38 MAPK 

分 类 号：R967[医药卫生—药理学]