南方医科大学学报2025，Vol.45Issue(4)：765-773,9.DOI:10.12122/j.issn.1673-4254.2025.04.12
4-(芳基乙炔基)-吡咯并[2,3-d]嘧啶通过抑制mGluR5调控ERK1/2-SGK1信号通路改善小鼠创伤后应激障碍
4-(Arylethyl)-pyrrolo[2,3-d]pyrimidine improves post-traumatic stress disorder in mice by inhibiting mGluR5-regulated ERK1/2-SGK1 signaling pathway
摘要
Abstract
Objective To observe the effect of 4-(arylethynyl)-pyrrolo[2,3-d]pyrimidine(10b)on post-traumatic stress disorder(PTSD)-like behaviors and ERK1/2-SGK1 signaling pathway in mice.Methods C57BL/6 mouse models exposed to single prolonged stress(SPS)were treated with daily gavage of saline,10b at low,moderate and high doses,or paroxetine for 14 days.The changes in PTSD-like behaviors of SPS mice with different treatments were observed using behavioral tests.Western blotting and immunofluorescence assay were used to detect the protein expression levels of mGluR5,p-ERK,and SGK1 in the hippocampus of the mice.Pathological changes in the liver and kidney tissues of the mice were examined using HE staining.Molecular docking and molecular dynamics analyses were employed to evaluate the binding stability between the compound 10b and mGluR5.Results Compared to the normal control mice,the SPS mice exhibited obvious PTSD-like behaviors with increased hippocampal expressions of mGluR5 and p-ERK proteins and decreased SGK1 protein expression.Compound 10b significantly ameliorated behavioral abnormalities in SPS mice,inhibited mGluR5 expression,and reversed the dysregulation of p-ERK and SGK1.No obvious liver or kidney toxicity was observed after 10b treatment.Molecular docking and dynamics studies demonstrated a stable interaction between 10b and mGluR5.Conclusion The compound 10b ameliorates PTSD-like behaviors induced by SPS in mice possibly by inhibiting mGluR5 expression to modulate the ERK1/2-SGK1 signaling pathway.关键词
4-(芳基乙炔基)-吡咯并[2,3-d]嘧啶/创伤后应激障碍/代谢型谷氨酸受体5/单一长时程应激/ERK1/2/SGK1Key words
4-(arylethynyl)-pyrrolo[2,3-d]pyrimidine/post-traumatic stress disorder/metabotropic glutamate receptors 5/single prolonged stress/ERK1/2/SGK1引用本文复制引用
何存宝,杨绍杰,朱国旗..4-(芳基乙炔基)-吡咯并[2,3-d]嘧啶通过抑制mGluR5调控ERK1/2-SGK1信号通路改善小鼠创伤后应激障碍[J].南方医科大学学报,2025,45(4):765-773,9.基金项目
国家自然科学基金(82404890) （82404890）
安徽省自然科学基金(2208085MH282) （2208085MH282）
安徽省高等学校科学研究项目(2024AH040137,2024AH051044) （2024AH040137,2024AH051044）
新安医学与中医药现代化研究所"揭榜挂帅"项目(2023CXMMTCM013) Supported by National Natural Science Foundation of China(82404890). （2023CXMMTCM013）
