中国药房2026，Vol.37Issue(11)：1440-1446,7.DOI:10.6039/j.issn.1001-0408.2026.11.10
温阳解郁颗粒调控NLRP3/ASC/Caspase-1通路对大鼠的抗抑郁作用机制研究
Mechanism of Wenyang jieyu granules regulating NLRP3/ASC/Caspase-1 pathway on antidepressant effect in rats
摘要
Abstract
OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules(WYJYG)via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/Caspase-1 pathway.METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group,model group,MCC950(NLRP3 inflammasome inhibitor)group(10 mg/kg),fluoxetine group(positive control,2.08 mg/kg),low-dose WYJYG(3.78 g/kg)and high-dose WYJYG group(7.56 g/kg),with 10 rats in each group.From the 22nd day of the experiment,rats in the fluoxetine group,low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline.Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water.Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection.All interventions were performed once a day for 21 consecutive days.Behavioral tests were conducted once a week.After the last administration,the contents of ASC,ionized calcium binding adaptor molecule 1(Iba1),interleukin-1β(IL-1β),and IL-18 in hippocampal tissues were detected.The protein expressions of NLRP3,cluster of differentiation 68(CD68),Caspase-1,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein were determined,and neuronal apoptosis was observed.RESULTS After the last administration,compared with the model group,the open-field activity time was significantly prolonged(P＜0.05),and the latency to feed in a novel environment was significantly shortened(P＜0.05)in rats of the high-dose WYJYG group.In hippocampal tissue,the contents of ASC,Iba1,IL-1β,and IL-18,as well as the protein expression levels of NLRP3,Caspase-1,and CD68,and the positive rate of neuronal apoptosis were all significantly decreased/downregulated(P＜0.05).Bcl-2 protein expression was significantly upregulated(P＜0.05),and the density of neuronal apoptosis-positive cells was significantly reduced(P＜0.05).CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway,reducing microglia-mediated neuroinflammation,and inhibiting hippocampal neurons apoptosis.关键词
温阳解郁颗粒/抑郁症/NLRP3炎症小体/凋亡相关斑点样蛋白/胱天蛋白酶1/神经炎症/神经元Key words
Wenyang jieyu granules/depression/NLRP3 inflammasome/ASC/Caspase-1/neuroinflammation/neurons分类
医药卫生引用本文复制引用
孟霜,赵杰,王鑫鑫,谭丹丹,周晓荣,孙慧敏,马小娟,冯振宇..温阳解郁颗粒调控NLRP3/ASC/Caspase-1通路对大鼠的抗抑郁作用机制研究[J].中国药房,2026,37(11):1440-1446,7.基金项目
山西省中医药管理局科研课题(No.2023ZYYA020) （No.2023ZYYA020）
经方扶阳山西省重点实验室项目(No.202504010931053) （No.202504010931053）
山西省中医药管理局科研课题(No.2023ZYYA2006) （No.2023ZYYA2006）
山西省卫生健康委科研课题(No.2024132) （No.2024132）
