多吡啶铱配合物在体内外对白色念珠菌的杀灭作用  

Killing Activity of Polypyridine Iridium Complex on Candida albicans in vitro and in vivo

作　　者：付琛[1] 周伟 赵梓圳 付爱玲[1] FU Chen;ZHOU Wei;ZHAO Zizhen;FU Ailing(School of Pharmaceutical Sciences,Southwest University,Chongqing 400715,China)

机构地区：[1]西南大学药学院,重庆400715

出　　处：《西南大学学报（自然科学版）》2022年第12期70-76,共7页Journal of Southwest University(Natural Science Edition)

基　　金：国家自然科学基金资助项目(82073830);重庆市基础科学和前沿资助项目(cstc2018jcyjAX0612).

摘　　要：白色念珠菌(Candida albicans)感染性疾病是一种常见的人畜共患性疾病,研发具有抗白色念珠菌活性的创新药物将有助于大力推动临床治疗的发展.该研究将确定一种带有荧光的多吡啶类配合物可进入白色念珠菌细胞中,在体内外显示出具有较强的杀灭该真菌的效果,该研究为临床治疗白色念珠菌感染性肾炎提供一个新的方法,通过荧光观测方法,检测白色念珠菌可摄取配合物,然后使用亚甲基蓝染色确定配合物对白色念珠菌的杀灭作用;通过量效关系和时效关系研究进一步验证配合物的抗菌活性,测定出配合物杀灭白色念珠菌的最小抑菌质量浓度(minimum inhibitory concentration,MIC)和最小杀菌质量浓度(minimum fungicidal concentration,MFC);在白色念珠菌感染的肾炎模型中,评价配合物在体内的抑菌效果.结果表明,配合物具有较强的抗菌作用,对白色念珠菌的MIC和MFC分别为1μg/mL和2μg/mL,抗菌活性强于临床药物氟康唑.此外,配合物可降低动物模型肾脏中的白色念珠菌负载量,减轻肾脏炎症损伤,表现出较好的治疗效果.Candida albicans infection is a common zoonotic disease.The development of innovative drugs with anti-Candida albicans activity will help to vigorously promote the development of clinical treatment.This study will determine that a fluorescent polypyridine complex can enter Candida albicans cells,and show a strong effect of killing the fungus in vivo and in vitro,which will provide a new method for the clinical treatment of Candida albicans infectious nephritis.The intracellular uptake of the complex by Candida albicans was detected by using fluorescence observation,and then the anti-Candida albicans effect of the complex was determined by methylene blue staining.The antifungal activity of the complex was further verified by the study of relationships of dose-effect and time-effect.The minimum inhibitory concentration(MIC)and minimum fungicidal concentration(MFC)of the complex to kill Candida albicans also were determined.Moreover,the antifungal effect of the complex in vivo was evaluated in the nephritis model of Candida albicans infection.The results Showed:The MIC and MFC of the complex against Candida albicans were 1μg/mL and 2μg/mL,respectively.The antifungal activity of the complex was stronger than that of fluconazole.In addition,the complex could reduce Candida albicans load in the kidney of animal model,and decrease renal inflammatory injury,showing the therapeutic effect.

关 键 词：白色念珠菌 多吡啶铱配合物 感染性肾炎 抗真菌活性 

分 类 号：Q936[生物学—微生物学] R978.7[医药卫生—药品]