C1q中和抗体可通过C1q/C3通路改善小鼠的产后抑郁样行为

doi:10.12122/j.issn.1673-4254.2025.10.07

摘要/Abstract

摘要：

目的探究补体系统经典途径的启动因子C1q对产后小鼠抑郁样行为的影响以及C1q中和抗体对产后小鼠抑郁样行为的改善作用及其机制。方法构建产后抑郁小鼠模型，分成对照组及激素模拟妊娠小鼠（HSP）产后抑郁模型组。行为学结果检测小鼠抑郁样行为，ELISA试剂盒及Western blotting检测C1q外周血含量及海马脑区表达，免疫荧光检测C1q与小胶质细胞共标情况，RNA测序分析HSP小鼠海马脑区基因表达差异，爱丁堡产后抑郁量表筛选产后抑郁患者，提取患者外周血单个核细胞，WB检测C1q水平。海马脑区立体定位注射C1q中和抗体，分成3组：对照组+IgG（CON+IgG）、模型组+IgG（HSP+IgG）、模型组+C1q Ab（HSP+C1q Ab），检测HSP小鼠抑郁样行为及海马脑区C3表达情况。结果与对照组相比，HSP小鼠表现出抑郁行为，糖水偏好率显著降低（P<0.05），强迫游泳及悬尾不动时间增加（P<0.05），外周血C1q含量（P<0.05）和海马脑区C1q水平表达增加（P<0.05）并伴随海马区Iba1与C1q共标增加（P<0.05）；产后抑郁患者外周单个核细胞C1q水平表达增加（P<0.05）；海马脑区立体定位注射C1q中和抗体缓解HSP小鼠抑郁样行为，与HSP+IgG组相比，HSP+C1q Ab组糖水偏好率显著增加（P<0.05），强迫游泳及悬尾不动时间减少（P<0.05），海马脑区C3表达降低（P<0.05），外周血促炎因子IL-6、TNF-α含量降低（P<0.05）。结论 C1q中和抗体可能通过C1q/C3信号通路改善产后抑郁小鼠抑郁样行为。

关键词: 补体C1q, 补体C3, 中和抗体, 小胶质细胞, 产后抑郁

Abstract:

Objective To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. Methods Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. Results The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. Conclusion C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.

Key words: complement C1q, complement C3, neutralizing antibody, microglia, postpartum depression

孙一鸣, 徐昕冉, 卓雪瑞, 蔡慧, 王艳. C1q中和抗体可通过C1q/C3通路改善小鼠的产后抑郁样行为[J]. 南方医科大学学报, 2025, 45(10): 2111-2117.

Yiming SUN, Xinran XU, Xuerui ZHUO, Hui CAI, Yan WANG. C1q-neutralizing antibodies improves postpartum depressive-like behaviors in mice by regulating the C1q/C3 pathway[J]. Journal of Southern Medical University, 2025, 45(10): 2111-2117.

图/表 7

图1 激素模拟妊娠小鼠产后抑郁模型制备

Fig.1 Preparation of the post pattern depression mouse model. A: The preparation process of the postpartum depression model. B: The preparation process of the postpartum depression model and stereotactic injection of C1q neutralizing antibody in the hippocampal brain region.

图2 激素模拟妊娠小鼠产后抑郁模型的评估

Fig.2 Evaluation of postpartum depression model in mice with hormone-simulated pregnancy (HSP). A-C: Sucrose preference test, tail suspension test and forced swimming test for evaluation of depressive-like behaviors of the mice. *P<0.05, **P<0.01 vs CON.

图3 HSP小鼠海马脑区C1q表达情况

Fig.3 Expression of C1q in the hippocampus of HSP mice. A: RNA sequencing for analyzing differentially expressed mRNAs. B: Serum C1q level of the mice. C, D: Expression of C1q in different brain regions. *P<0.05, **P<0.01 vs CON.

图4 HSP小鼠海马脑区C1q与Iba1共标情况

Fig.4 Co-labeling of C1q and Iba1 in the hippocampus of HSP mice. A: Immunofluorescence staining for detecting co-labeling of C1q and Iba1 in the hippocampus (Scale bar=100 μm). B: Quantitative analysis of C1q and Iba1 co-labeling in control and HSP mice. *P<0.05 vs CON.

图5 产后抑郁患者外周血C1q水平

Fig.5 Peripheral blood C1q level (A) and expression of C1q in peripheral blood mononuclear cells (B, C) in patients with postpartum depression. *P<0.05 vs CON.

图6 海马脑区立体定位注射C1q中和抗体评估HSP小鼠抑郁样行为

Fig.6 Effect of stereotactic injection of C1q-neutralizing antibody in the hippocampus on depressive-like behaviors of HSP mice. A-C: Sucrose preference test, tail suspension test and forced swimming test for evaluation of depressive-like behaviors of the mice. *P<0.05 vs CON+IgG, **P<0.01 vs CON+IgG, #P<0.05 vs CON+C1q Ab.

图7 海马脑区立体定位注射C1q中和抗体HSP小鼠C3及促炎因子水平

Fig.7 Hippocampal expression level of C3 and serum levels of pro-inflammatory factors in HSP mice following stereotactic injection of C1q-neutralizing antibody in the hippocampus. A, B: Expression of C3 in different brain regions of the mice detected by Western blotting. C: Serum IL-6 level. D: Serum TNF-α level. **P<0.01 vs CON+IgG, #P<0.05 vs CON+C1q Ab, ##P<0.01 vs CON+C1q Ab.

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