目的 探討紅景天苷對(duì)脂多糖（LPS）誘導(dǎo)炎癥抑郁模型小鼠的作用及機(jī)制。方法 48只Balb/c小鼠隨機(jī)分為對(duì)照組、模型組、鹽酸氟西?。?yáng)性藥，20 mg/kg）組、紅景天苷（25 mg/kg）組，每組12只。各組連續(xù)ig給藥14 d后，除對(duì)照組外，其余各組ip 1 mg/kg LPS連續(xù)7 d制備抑郁癥模型。以糖水偏好實(shí)驗(yàn)、曠場(chǎng)實(shí)驗(yàn)、懸尾實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)檢測(cè)小鼠抑郁樣癥狀；結(jié)束后取腦組織與血液檢測(cè)腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1β（IL-1β）水平；Iba1免疫熒光染色檢測(cè)腦組織小膠質(zhì)細(xì)胞激活；Western blotting法檢測(cè)腦組織TLR4信號(hào)通路蛋白TLR4、NLRP3、cleaved-Caspase-1/Caspase-1表達(dá)。結(jié)果 與模型組比較，紅景天苷與鹽酸氟西汀預(yù)防給藥能夠顯著上調(diào)小鼠糖水?dāng)z取率（P<0.05），增加小鼠穿格評(píng)分（P<0.05），下調(diào)懸尾與強(qiáng)迫游泳不動(dòng)時(shí)間（P<0.05）；顯著逆轉(zhuǎn)LPS造成的TNF-α、IL-1β水平上調(diào)（P<0.05）；明顯抑制小膠質(zhì)細(xì)胞激活，顯著降低Iba1熒光強(qiáng)度（P<0.05）；顯著降低腦組織中TLR4、NLRP3與cleaved-Caspase-1/Caspase-1蛋白表達(dá)（P<0.05）。結(jié)論 ip LPS成功構(gòu)建了炎癥誘導(dǎo)的抑郁模型，紅景天苷通過(guò)TLR4信號(hào)通路調(diào)控小膠質(zhì)細(xì)胞激活，從而改善小鼠抑郁樣行為。

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-α and IL-1β induced 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 ipinjection of LPS. Salidroside regulates the activation of microglia through the TLR4 signaling pathway, and successfully improves depression-like behavior in mice.

R285.5

海南省衛(wèi)生計(jì)生行業(yè)科研項(xiàng)目（16A200062）