南方医科大学学报2025,Vol.45Issue(3):577-586,10.DOI:10.12122/j.issn.1673-4254.2025.03.15
菊淀粉型巴戟天寡糖降低肺炎链球菌脑膜炎小鼠的症状评分和死亡率
Therapeutic effects of inulin-type oligosaccharides of Morinda officinalis on Streptococcus pneumoniae meningitis in mice
摘要
Abstract
Objective To investigate the therapeutic effects of inulin-type oligosaccharides of Morinda officinalis(IOMO)in a murine model of Streptococcus pneumoniae meningitis(SPM)and explore its possible mechanisms.Methods A total of 120 male C57BL/6J mice were randomly assigned into Sham,SPM+Saline,SPM+IOMO(25 mg/kg),and SPM+IOMO(50 mg/kg)groups.After modeling,the mice received daily gavage of saline or IOMO at the indicated doses for 7 consecutive days,and the changes in symptom scores and mortality of the mice were monitored.Brain pathology and neuronal injury of the mice were assessed using HE and Nissl staining,and qRT-PCR was performed to detect mRNA levels of the inflammatory mediators.Brain edema and blood-brain barrier(BBB)permeability of the mice were evaluated by measuring brain water content and Evans blue(EB)staining;Western blotting was used to analyze the expressions of BBB-associated proteins,and flow cytometry was employed to detect IFN-γ expression level in the infiltrating lymphocytes.Open-field test(OFT)and novel object recognition test(NORT)were conducted to assess learning and memory ability of the mice on day 21 after modeling.Results IOMO treatment at 50 mg/kg significantly reduced the symptom scores and mortality rate of SPM mice,alleviated brain damage,and downregulated mRNA levels of IL-6,TNF-α,IL-1β,IL-18,IFN-γ,iNOS,NLRP3,ASC,caspase-1 and GSDMD in the brain tissue.IOMO treatment also decreased brain water content and EB leakage,upregulated VE-cadherin and occludin expressions,and suppressed AQP4,iNOS,and IFN-γ levels of the mice.IOMO-treated mice exhibited improved learning and memory compared with the saline-treated mice on day 21 after SPM modeling.Conclusion IOMO alleviates SPM symptoms,reduces mortality,and mitigates cognitive deficits in mice possibly by suppressing cerebral inflammation and protecting BBB functions.关键词
菊淀粉型巴戟天寡糖/脑膜炎/肺炎链球菌/血脑屏障/干扰素-γKey words
inulin-type oligosaccharides of Morinda officinalis/meningitis/Streptococcus pneumoniae/blood-brain barrier/interferon-γ引用本文复制引用
李泽涵,梁萌,韩根成,张学武..菊淀粉型巴戟天寡糖降低肺炎链球菌脑膜炎小鼠的症状评分和死亡率[J].南方医科大学学报,2025,45(3):577-586,10.基金项目
国家自然科学基金(82171753,82371776) Supported by National Natural Science Foundation of China(82171753,82371776). (82171753,82371776)