广西医科大学学报2023，Vol.40Issue(12)：1956-1963,8.DOI:10.16190/j.cnki.45-1211/r.2023.12.004
绿原酸联合伏立康唑对大鼠侵袭性肺曲霉病的干预效果及免疫机制
Intervention effect of chlorogenic acid combined with voriconazole on invasive pulmonary as-pergillosis in rats and its immune mechanism
摘要
Abstract
Objective:To explore the intervention effect of chlorogenic acid(CRA)combined with voriconazole(VRC)on invasive pulmonary aspergillosis in vivoand its immune mechanism.Methods:The rats were divided into normal control group,model group,CRA group,VRC group,and combined treatment group(CRA+VRC group).After the successful establishment of the rat model of invasive pulmonary aspergillosis,the normal con-trol group and the model group were treated with normal saline,and the other groups were given CRA alone,VRC alone and combination of the two drugs for 7 days.The general condition of rats was observed to evaluate the severity of systemic infection.The fungal load in lung tissue and galactomannan(GM)content in alveolar la-vage fluid were measured.Hematoxylin-eosin(HE)staining and periodic acid-silver methenamine(PASM)staining were used to observe the pathologi-cal changes of lung infection.The protein expression levels of CD68,inducible nitric oxide synthase(iN-OS)and Arginase 1(Arg-1)were detected by immu-nohistochemistry.Enzyme-linked immunosorbent as-say(ELISA)was used to detect the levels of M1 phe-notype cytokines tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and M2 phenotype cytokines IL-10 of macrophages in lung tissue homogenate.Results:Compared with the model group,the CRA+VRC group had the best general condition,and the trend of weight loss was significantly slowed down(P＜0.05),and the fungal load and GM concentration in alveolar lavage fluid were significantly reduced(P＜0.01).The pulmonary vessels and bronchus of the lung tissue of rats in the model group were obviously invaded by fungi,a large number of myce-lia and spores grew,and there was extensive inflammation and hemorrhage,while in the lung tissue of rats in the CRA+VRC group,mycelia was significantly reduced and the damage was light.Compared with the model group,the expression levels of CD68 and Arg-1 protein in the lung tissue of rats in the CRA+VRC group were signifi-cantly decreased(P＜0.01),and the expression level of iNOS protein was significantly increased(P＜0.05).The levels of TNF-α and IL-6 in lung tissue were significantly increased(P＜0.05,P＜0.01).Conclusion:CRA com-bined with VRC has a synergistic therapeutic effect on invasive pulmonary aspergillosis model rats,and its mech-anism may be related to CRA promoting the phenotype polarization of macrophage M1.关键词
绿原酸/伏立康唑/侵袭性肺曲霉病/巨噬细胞/极化/细胞因子Key words
chlorogenic acid/voriconazole/invasive pulmonary aspergillosis/macrophages/polarization/cyto-kine分类
医药卫生引用本文复制引用
杨婷,罗劲,刘晓彤,冯羿植,孔晋亮..绿原酸联合伏立康唑对大鼠侵袭性肺曲霉病的干预效果及免疫机制[J].广西医科大学学报,2023,40(12):1956-1963,8.基金项目
国家自然科学基金资助项目(No.82104499 （）
No.82160783) （）
广西科技厅重点研发计划项目(No.桂科AB21196010) （No.桂科AB21196010）
中国博士后科学基金第73批面上资助项目(No.2023MD734158) （No.2023MD734158）
广西自然科学基金青年科学基金资助项目(No.2023GXNSFBA026146) （No.2023GXNSFBA026146）
广西医科大学第一附属医院临床研究攀登计划青年科技启明星计划资助项目(No.YYZS2020016) （No.YYZS2020016）
广西卫健委自筹经费科研课题青年基金项目(No.Z20200825) （No.Z20200825）
