BAP31对急性炎症中M1型巨噬细胞的影响及其机制分析OA
The effect and mechanism analysis of BAP31 on M1 macrophages in acute inflammation
目的:探讨B细胞相关受体蛋白31(BAP31)对急性炎症中M1型巨噬细胞的调控作用.方法:将Lyz2Cre-BAP31flox/flox和BAP31flox/flox小鼠采用腹腔注射给予小鼠脂多糖(lipopolysaccharide,LPS),构建急性炎症小鼠模型,评估LPS对各组小鼠体质量、结肠长度的影响.从BAP31flox/flox和Lyz2Cre-BAP31flox/flox小鼠股骨中提取骨髓细胞,进行体外实验,经10%L929小鼠成纤维细胞上清液诱导为巨噬细胞后,利用RT-qPCR法及Western blot法检测巨噬细胞极化的相关基因及蛋白的表达情况.结果:在急性炎症模型中,与PBS注射的Lyz2Cre-BAP31flox/flox小鼠相比,Lyz2Cre-BAP31flox/flox小鼠经LPS注射72 h后,出现体质量下降,结肠的长度明显变短;结肠组织黏膜出现不同程度的炎症细胞浸润及腺体明显萎缩.体外实验中Lyz2Cre-BAP31flox/flox小鼠骨髓来源的巨噬细胞,与BAP31flox/flox小鼠骨髓来源的巨噬细胞相比,经LPS或γ干扰素(IFNγ)或LPS+IFNγ刺激后M1型巨噬细胞的相关基因表达明显增加;M2型巨噬细胞的相关基因表达显著下降.Western blot实验结果表明BAP31敲低后可上调p-STAT1和p-ERK的蛋白表达水平.结论:BAP31敲低后通过调控STAT1和ERK的磷酸化水平进而影响M1型巨噬细胞活化,为预防和治疗急性炎症提供新的靶点.
Objective:To investigate the regulatory effect of B cell associated receptor protein 31(BAP31)on M1 macrophages in acute inflammation.Methods:Lyz2Cre-BAP31flox/flox and BAP31flox/flox mice were intraperitoneally injected with lipopolysaccharide(LPS)to establish an acute inflammation mouse model,and the effects of LPS on body weight and colon length of each group were evaluated.Bone marrow cells were extracted from the femurs of BAP31flox/flox and Lyz2Cre-BAP31flox/flox mice for in vitro experiments.After induction into macrophages using 10%L929 mouse fibroblast supernatant,the expression of genes and proteins related to macrophage polarization was detected by RT-qPCR and Western blot.Results:In the acute inflammation model,compared with Lyz2Cre-BAP31flox/flox mice injected with PBS,Lyz2Cre-BAP31flox/flox mice injected with LPS for 72 h showed decreased body weight and significantly shortened colon length.There was a large amount of inflammatory cell infiltration and significant glandular atrophy in the intestinal mucosa.In vitro experiments showed that bone marrow-derived macrophages from Lyz2Cre-BAP31flox/flox mice,compared to those from BAP31flox/flox mice,showed significantly increased expression of M1 macrophage-related genes after stimulation with LPS,IFNγ,or LPS+IFNγ,while M2 macrophage-related genes was significantly decreased.Western blot results showed that BAP31 knockdown upregulated the protein expression levels of p-STAT1 and p-ERK.Conclusion:Knockdown of BAP31 affects M1 macrophage activation by regulating the phosphorylation levels of STAT1 and ERK,providing a new target for the prevention and treatment of acute inflammation.
贺娟;韩竹军;赵千玉;张珉;王旭光;薄威;王晓开;张忠;王晓宇
沈阳医学院基础医学院病理学教研室,辽宁 沈阳 110034沈阳医学院基础医学院病理学教研室,辽宁 沈阳 110034沈阳医学院基础医学院病理学教研室,辽宁 沈阳 110034沈阳医学院基础医学院病理学教研室,辽宁 沈阳 110034沈阳市肿瘤进展关键标志物筛查与靶向治疗重点实验室辽宁省张忠劳模创新工作室沈阳医学院基础医学院病理学教研室,辽宁 沈阳 110034沈阳市肿瘤进展关键标志物筛查与靶向治疗重点实验室辽宁省张忠劳模创新工作室
医药卫生
B细胞相关受体蛋白31巨噬细胞急性炎症
BAP31macrophageacute inflammation
《沈阳医学院学报》 2026 (1)
9-17,9
国家自然科学基金青年基金(No.82400695)辽宁省联合基金项目面上项目(No.2023-MSLH-298)辽宁省教育厅课题(No.LJ212410164016)辽宁省科技计划联合计划博士科研启动项目(No.2024-BSLH-295)
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