Found programs: Natural Science Research Project of Anhui Educational Committee ( No . KJ2020A0180) ; Pro- vincial Graduate Academic Innovation Project of Anhui Provincial Department of Education ( No . 2022xscx059) ; Health Research Project of Anhui Province (No . AHWJ2023A20229) ; Provincial Graduate Education and Teach- ing Reform Research Project of Anhui Provincial Department of Education (No . 2022jyjxggyj226) ; National Natu- ral Science Foundation Incubation Plan of the Second Affiliated Hospital of Anhui Medical University ( No . 2019GQFY04) ; Science and Technology Nova Incubation Project of the Second Affiliated Hospital of Anhui Medi- cal University (No . 2018KA08) ; Outstanding Young Core Teachers Overseas Visiting Project for Colleges and Uni- versities in Anhui Province (No . gxgwfx2020024)
Authors：Li Yuanping1 , Tan Hui 1 , Meng Jingyuan1 , Yang Yan1 , Ma Tengteng1 , Yang Zhengmao2 , Ma Jiaqing1 , Xie Jianping3 , Guo Ying1
Keywords：Card9 ; Aspergillus fumigatus; macrophage; inflammatory factor; keratitis
DOI：10.19405/j.cnki.issn1000-1492.2025.03.008
〔Abstract〕 Abstract Objective To investigate the therapeutic effects and underlying mechanisms of cannabidiol (CBD) and its nano-formulations on depression-like behaviors in mice . Methods A murine model of acute anxiety and depres- sion was established by intraperitoneal administration of lipopolysaccharide ( LPS) . A total of 55 mice were ran- domly assigned into several groups : for the long-term study , a control group (Con) , a model group (LPS) , a can- nabidiol group (CBD) , a nano-cannabidiol group (NCBD) , and a sertraline (SER) group , each consisting of 7 mice . In the short-term study , mice were divided into four groups : the Con group , LPS group , CBD group , and NCBD group , with 5 mice in each group . Except for the Con group and LPS group , which were given distilled wa- ter , the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulation via oral ga- vage . The open field and forced swimming tests were employed to assess anxiety- and depression-like behaviors in immune cells . The expression of Card9 in the cornea of mice treated with Card9 siRNA was significantly reduced . After inhibiting the expression of Card9 gene , the expressions of Card9 , NF-κB , IL-1β, IL-6 and TNF-αsignifi- cantly decreased and the changes of IL-1βwere most significant. In in vitro studies , Card9 exhibited negligible ex- pression in human corneal epithelial cells , contrasting with its pronounced expression in THP-1 cells . After the in- duction of macrophages , Card9 , NF-κB , IL-1β, IL-6 , and TNF-αwere significantly upregulated under the stimu- lation of A. fumigatus . After inhibiting the expression of Card9 , the stimulated expression of these factors was sig- nificantly reduced , with the most notable change observed in IL-1β. Conclusion Card9 is involved in the inflam- matory development and healing process of A. fumigatus keratitis . Card9 deficiency can cause functional impair- ment of macrophages and inhibit the expression of inflammatory factors to a certain extent , in which IL-1βhas the greatest effect.