红景天苷介导TLR4调控小胶质细胞激活对小鼠抑郁样行为的改善作用  

Salidroside improves depression-like behavior in mice through TLR4 mediated microglia activation

作　　者：莫菁莲[1] 陈思丹[1] 符乃光[2] 王政[3] MO Jinglian;CHEN Sidan;FU Naiguang;WANG Zheng(Pharmaceutical Department of Hainan Provincial People's Hospital,Hainan Hospital Affiliated to Hainan Medical College,Haikou 570311,China;School of Pharmacy,Hainan Medical College,Haikou 571101,China;Laboratory of Biotechnology and Biochemistry,Hainan Medical College,Haikou 571101,China)

机构地区：[1]海南省人民医院药学部,海南医学院附属海南医院,海南海口570311 [2]海南医学院药学院,海南海口571101 [3]海南医学院生物技术与生物化学实验室,海南海口571101

出　　处：《药物评价研究》2021年第9期1869-1875,共7页Drug Evaluation Research

基　　金：海南省卫生计生行业科研项目(16A200062)。

摘　　要：目的探讨红景天苷对脂多糖(LPS)诱导炎症抑郁模型小鼠的作用及机制。方法48只Balb/c小鼠随机分为对照组、模型组、盐酸氟西汀(阳性药,20 mg/kg)组、红景天苷(25 mg/kg)组,每组12只。各组连续ig给药14 d后,除对照组外,其余各组ip 1 mg/kg LPS连续7 d制备抑郁症模型。以糖水偏好实验、旷场实验、悬尾实验和强迫游泳实验检测小鼠抑郁样症状;结束后取脑组织与血液检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平;Iba1免疫荧光染色检测脑组织小胶质细胞激活;Western blotting法检测脑组织TLR4信号通路蛋白TLR4、NLRP3、cleaved-Caspase-1/Caspase-1表达。结果与模型组比较,红景天苷与盐酸氟西汀预防给药能够显著上调小鼠糖水摄取率(P<0.05),增加小鼠穿格评分(P<0.05),下调悬尾与强迫游泳不动时间(P<0.05);显著逆转LPS造成的TNF-α、IL-1β水平上调(P<0.05);明显抑制小胶质细胞激活,显著降低Iba1荧光强度(P<0.05);显著降低脑组织中TLR4、NLRP3与cleaved-Caspase-1/Caspase-1蛋白表达(P<0.05)。结论ip LPS成功构建了炎症诱导的抑郁模型,红景天苷通过TLR4信号通路调控小胶质细胞激活,从而改善小鼠抑郁样行为。Objective To investigate the effect of salidroside on LPS-induced depression in mice and the mechanism through inflammation.Methods 48 Balb/c mice were randomly divided into control group,model group,fluoxetine group(20 mg/kg),salidroside group(25 mg/kg),12 mice in each group.After 14 days of continuous ig administration,mice in each group were ip injected with 1 mg/kg LPS or saline for 7 days.The sucrose preference test,open field test,tail suspension test and forced swimming test were used to detect depression-like symptoms in mice.At the end,the brain tissue and blood were taken for inflammatory cytokines detection,Immunofluorescence staining was applied for microglia activation test,and Western Blotting was used to detect the protein expression of TLR4 signaling pathway.Results Compared with model group,salidroside and fluoxetine hydrochloride pre administration could significantly increase the rate of sugar water intake(P<0.05),increase the grid score(P<0.05),and reduce the immobility time of tail suspension and forced swimming(P<0.05);significantly reversed the up-regulation of TNF-αand IL-1βinduced by LPS(P<0.05);Significantly inhibited the activation of microglia and significantly reduced the fluorescence intensity of Iba1(P<0.05);The expression of TLR4,NLRP3 and cleaved-caspase-1/caspase-1 protein in brain tissue was significantly decreased(P<0.05).Conclusion The inflammation-induced depression model was successfully constructed by ip injection of LPS.Salidroside regulates the activation of microglia through the TLR4 signaling pathway,and successfully improves depression-like behavior in mice.

关 键 词：红景天苷 抑郁症 小胶质细胞 脂多糖 炎症反应 TOLL样受体4 NLRP3 CASPASE-1 

分 类 号：R285.5[医药卫生—中药学]