烟碱型乙酰胆碱受体α7亚型在产后抑郁中的作用机制研究

The mechanism of nicotinic acetylcholine receptorα7 subtype in postpartum depression

目的探讨烟碱型乙酰胆碱受体α7亚型(α7nAChR)在产后抑郁(PPD)中的作用机制。方法使用激素模拟妊娠(HSP)诱导的PPD小鼠模型,并将小鼠分为4组对照组、PPD组、PNU282987组和PNU282987+α7nAChR inhibitor组。对小鼠进行悬尾试验和强迫游泳试验以评估抑郁样行为。分别通过Nissl染色和免疫荧光染色检测海马CA1区神经细胞和α7nAChR表达。通过蛋白质印迹分析NLRP3炎症小体激活情况。结果与PPD组相比,PNU282987组鼠海马组织中α7nAChR表达和海马区的神经细胞数量显著增加(P<0.01),和尾悬测试和强迫游泳测试中的不动时间显著降低(P<0.01);PNU282987组小鼠海马组织中NLRP3、NF-κB、pro-IL-1β、cleaved-caspase 1和IL-1β表达较PPD组显著降低(P<0.05);与PNU282987组小鼠相比,PNU282987+α7nAChR inhibitor组小鼠在尾悬测试和强迫游泳测试中的不动时间显著增加(P<0.01),且海马区的神经细胞数量显著降低(P<0.05);此外,α7nAChR inhibitor逆转了PNU282987对PPD小鼠海马组织中NLRP3、NF-κB、pro-IL-1β、cleaved-caspase 1和IL-1β表达的抑制作用(P<0.05)。结论α7nAChR通过抑制NLRP3炎性体激活在PPD中发挥保护作用。

Objective To explore the mechanism ofα7 subtype of nicotinic acetylcholine receptors(α7nAChR)in postpartum depression(PPD).Methods A mouse model of PPD induced by hormone-simulated pregnancy(HSP)was used and the mice were divided into four groups:control group,PPD group,PNU282987 group and PNU282987+α7nAChR inhibitor group.Tail suspension test and forced swimming test were performed to evaluate depression-like behaviors.Nissl staining and immunofluorescence staining were used to detect the expression of neurons andα7nAChR in hippocampal CA1 area.The activation of NLRP3 inflammasome was analyzed by using Western blot.Results Compared with the PPD group,the expression ofα7nAChR and the number of neurons in the hippocampus of the PNU282987 group were increased significantly(P<0.01)and the immobility time in the tail suspension test and the forced swimming test was significantly reduced(P<0.01).The expressions of NLRP3,NF-κB,pro-IL-1β,cleaved-caspase 1,and IL-1βin the hippocampus of the PNU282987 group were significantly lower than those in the PPD group(P<0.05).Compared with the PNU282987 group,the immobility time of the mice in the PNU282987+α7nAChR inhibitor group in the tail suspension test and the forced swimming test was significantly increased(P<0.01),and the number of neurons in the hippocampus was significantly reduced(P<0.05).In addition,α7nAChR inhibitor was reversed the inhibitory effect of PNU282987 on the expression of NLRP3,NF-κB,pro-IL-1β,cleaved-caspase 1,and IL-1βin the hippocampus of PPD mice(P<0.05).Conclusionα7nAChR plays a protective role in PPD by inhibiting the activation of NLRP3 inflammasome.