辛伐他汀对脂多糖诱导的小鼠抑郁行为及神经炎症的影响  

Effect of simvastatin on lipopolysaccharides induced depressive behaviors and neuroinflammation in mice

作　　者：张海娜[1] 徐慧[1] 余旭奔 王晨之 许巧巧[1] 戴歌心[1] 胡卢丰[1] 张秀华[1] 

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325000 [2]温州市龙湾区第一人民医院药剂科,浙江温州325024

出　　处：《中国药理学通报》2017年第3期373-378,共6页Chinese Pharmacological Bulletin

基　　金：浙江省自然科学基金资助项目(No LY16H30005)

摘　　要：目的探讨辛伐他汀对脂多糖(LPS)诱导小鼠抑郁行为的影响及其机制。方法给予ICR小鼠单剂量腹腔注射脂多糖0.5 mg·kg^(-1)建立抑郁小鼠模型。在给予小鼠LPS前每天灌胃给予辛伐他汀,连续给药1周。采用强迫游泳实验、悬尾试验、糖水偏好度实验检测小鼠抑郁样行为;采用Western blot检测小鼠前额叶皮层NF-κB p65、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)蛋白水平。结果悬尾试验和强迫游泳实验结果显示,与正常对照组相比,LPS组小鼠不动时间明显延长,给予辛伐他汀10和20 mg·kg^(-1)能明显减少抑郁小鼠不动时间;糖水偏好度检测结果显示,与正常对照组相比,LPS组小鼠糖水偏好度明显降低,而给予辛伐他汀10和20 mg·kg^(-1)能增加抑郁小鼠糖水偏好度;Western blot结果显示,LPS组小鼠前额叶皮层NF-κB p65,IL-1β和TNF-α明显升高,给予辛伐他汀10和20 mg·kg^(-1)能抑制抑郁小鼠炎性蛋白表达升高。结论辛伐他汀能够改善LPS诱导的小鼠抑郁样行为和神经炎症。Aim Toinvestigatetheeffectsofsimvasta-tin on depressive behaviors and neuroinflammation in lipopolysaccharide （LPS）-induced depression in mice. Methods MalemicewereinjectedwithLPS（0.5mg ·kg-1 ）to induce depressive mice model.Before in-jecting LPS,mice were administered orally with simv-astatin consecutively for 7 days.Forced swimming test （FST）,tail suspension test （TST）,and sucrose pref-erence test （SPF）were used to detect depression-likebehaviors in mice,while Western blot was used to de-tect the proteins of pro-inflammatory factors nuclear factor-κB p65 subunit （NF-κB p65 ）,interleukin-1β（IL-1β）,tumor necrosis factor-α（TNF-α） in the prefrontalcortexofmice.Results ThedataofFST and TST showed that mice treated with LPS displayed increased immobility time,while depressed mice trea-ted with simvastatin 10,20 mg·kg-1 showed signifi-cant reduction in immobility time relative to mice trea-ted with LPS.The data of SPF showed decreased su-crose preference in mice treated with LPS,while simv-astatin 10,20 mg·kg-1 treatment suppressed the re-duction of sucrose preference in mice treated with LPS. The data of Western blot showed that treatment with LPS significantly increased the levels of NF-κB p65 , IL-1βand TNF-αin the prefrontal cortex of mice.However,simvastatin 10,20 mg·kg-1 suppressed the change of these proinflammatory factors.Conclusion Simvastatinimprovesthedepression-likebehaviorsand neuroinflammatory response in LPS-induced depressive mice.

关 键 词：辛伐他汀 抑郁症 炎症 脂多糖 NF-κB 前额叶皮层 

分 类 号：R-332[医药卫生] R322.81