雷公藤甲素对LPS诱导的抑郁模型小鼠的治疗缓解作用-东南大学学报医学版

雷公藤甲素对LPS诱导的抑郁模型小鼠的治疗缓解作用

单位：海南医学院第二附属医院睡眠心理科, 海南海口 570000

分类号：R749.4; R-33

出版年·卷·期（页码）：2023·42·第四期（578-583）

摘要：

目的:探讨雷公藤甲素(triptolide,TPL)对脂多糖(lipopolysaccharide,LPS)诱导的抑郁相关表型小鼠的治疗缓解作用及相关机制。方法:将32只雄性C57BL/6小鼠(6~7周龄)随机均分为4组,即对照组(PBS+Vehicle组)、TPL组(PBS+TPL组)、模型组(LPS+Vehicle组)、治疗组(LPS+TPL组)。利用LPS诱导抑郁模型小鼠。首先对各组小鼠进行行为学观察;利用ELISA法对各组小鼠海马区炎症因子(TNF-α、IL-6、IL-1β、IFN-γ)水平进行测定;利用免疫荧光染色对各组小鼠海马区Iba-1及GFAPs阳性细胞数进行检测;利用免疫荧光染色及免疫组化染色对各组小鼠海马区神经发生标志物(BrdU及DCX)进行检测。结果:与PBS+Vehicle组相比,PBS+TPL组小鼠行为学、海马区炎症因子、Iba-1及GFAPs阳性细胞数及神经发生均无明显改变(P＞0.05);LPS+Vehicle组小鼠表现出抑郁行为、海马区炎症因子增加、Iba-1和GFAPs阳性细胞数增加以及神经发生减少(均P＜0.001)。与LPS+Vehicle组相比,LPS+TPL组小鼠抑郁行为减轻、海马区炎症因子减少、Iba-1及GFAPs阳性细胞数减少及神经发生增加(均P＜0.05)。结论:TPL可通过降低LPS诱导的抑郁模型小鼠海马炎症反应并增加海马神经发生以发挥其对抑郁症的缓解作用。

Objective: To investigate the palliative effect of triptolide(TPL) in lipopolysaccharide(LPS) induced depression-associated phenotype mice and the related mechanism. Methods: Thirty-two male C57BL/6 mice(6-7 weeks old) were randomly divided into four groups: control group(PBS+Vehicle group), TPL group(PBS+TPL group), model group(LPS+Vehicle group), and treatment group(LPS+TPL group). Depression model mice were induced by LPS. Firstly, behavioral observation was made in each group of mice. The levels of inflammatory factors(TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus of each group were determined by ELISA. The number of Iba-1 and GFAPs positive cells in the hippocampus of each group was detected by immunofluorescence staining. Neurogenesis markers(BrdU and DCX) in the hippocampus of each group were detected by immunofluorescence and immunohistochemical staining. Results: Compared with PBS+Vehicle group, there were no significant changes in behavior, hippocampal inflammatory factors, the number of Iba-1 and GFAPs positive cells and neurogenesis in PBS+TPL group(P>0.05). Compared with PBS+Vehicle group, mice in LPS+Vehicle group showed depressive behavior, increased inflammatory factors in hippocampus, increased number of Iba-1 and GFAPs positive cells, and decreased neurogenesis(all P<0.001). Compared with LPS+Vehicle group, mice in LPS+TPL group had less depressive behavior, less inflammatory cytokines in hippocampus, less Iba-1 and GFAPs positive cells, and more neurogenesis(all P<0.05). Conclusion: TPL plays a palliative role in depression by reducing the hippocampal inflammatory response and increasing hippocampal neurogenesis in mice with depression induced by LPS.

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