柚皮素降低细菌性脑膜炎引起的神经炎症和神经元损伤

Naringenin reduces neuroinflammation and neuronal damage caused by bacterial meningitis

目的探讨柚皮素对细菌性脑膜炎小鼠的治疗作用。方法45只雄性C57BL/6小鼠按照随机数字法将小鼠分为非感染组、感染组和感染+柚皮素组3组,每组15只小鼠。非感染组小鼠不采用肺炎链球菌干预,感染组小鼠采用肺炎链球菌进行细菌性脑膜炎建模,感染+柚皮素组小鼠在细菌性脑膜炎建模后,腹腔注射100mg/kg柚皮素,持续7 d。取脑组织,进行GFAP和Iba1免疫荧光染色检测星形胶质细胞和小胶质细胞活化程度;TUNEL和Fluoro-Jade C染色法检测皮层神经元受损情况;RT-qPCR检测脑组织中炎性因子(IL-6和TNF-α)和趋化因子(CCL-2和CCL-3)的mRNA水平。结果肺炎链球菌感染致细菌性脑膜炎小鼠生存率显著降低,脑内星形胶质细胞和小胶质细胞的活化程度增加,皮质中神经元受损,脑组织中IL-6、TNF-α、CCL-2和CCL-3的mRNA水平升高,柚皮素处理对细菌性脑膜炎小鼠上述变化具有明显的抑制作用。结论柚皮素是细菌性脑膜炎的有效抑制剂。

Objective To investigate the therapeutic effect of naringenin on bacterial meningitis mice.Methods Forty-five male C57BL/6 mice were randomly divided into three groups(n=15 for each group):mice in non-infected group were not treated with streptococcus pneumoniae;mice in infected group,bacterial meningitis was modeled with Streptococcus pneumoniae;mice in infection+naringenin group were intraperitoneally injected with 100mg/kg naringenin for 7 consecutive days after bacterial meningitis modeling.The survival of mice was observed and recorded.The activation of astrocytes and microglia was observed by GFAP and Iba1 immunofluorescence staining,respectively.Cortical neuron damage was detected by TUNEL and Fluoro-Jade C staining.The mRNA levels of inflammatory cytokines(IL-6 and TNF-α)and chemokines(CCL-2 and CCL-3)in brain tissue were detected by RT-q PCR.Results Compared with the infected group,the survival rate of mice the infected+naringenin group was significantly higher,the activation degree of astrocytes and microglia in the brain was decreased,the damaged neurons in the cortex were reduced,and the m RNA levels of IL-6,TNF-α,CCL-2 and CCL-3 in the brain tissue were decreased.Conclusion Naringenin is an effective inhibitor of bacterial meningitis.