抑制11β-HSD1缓解棕榈酸诱导的反应性星形胶质细胞活化的机制研究

doi:10.3969/j.issn.1003-9198.2026.10.005

摘要/Abstract

摘要： 目的探究抑制11β-羟基类固醇脱氢酶1型(11β-HSD1)缓解棕榈酸诱导的反应性星形胶质细胞活化的分子机制。方法体外培养乳鼠海马组织来源的原代星形胶质细胞,分为对照组、棕榈酸处理组、棕榈酸联合BVT.2733处理组以及棕榈酸处理的11β-HSD1基因敲除细胞组。采用透射电镜、免疫荧光、逆转录实时荧光定量聚合酶链反应(RT-qPCR)及蛋白质印迹法检测细胞超微结构、形态、相关基因及蛋白表达水平。通过转录组测序与生物信息学分析筛选差异表达基因及通路。结果棕榈酸可诱导星形胶质细胞向A1型反应性表型转化,并激活NF-κB介导的炎症信号通路(P<0.05)。敲除11β-HSD1基因或使用BVT.2733可显著改善超微结构损伤,抑制A1型转化并减轻炎症反应(P<0.05)。转录组测序及基因富集分析(GSEA)提示,NF-κB信号通路可能是11β-HSD1调控星形胶质细胞功能的关键下游途径。结论抑制11β-HSD1可有效减轻星形胶质细胞的超微结构损伤、抑制A1型转化并缓解炎症反应,其可作为肥胖相关认知功能障碍干预的潜在靶点。

关键词: 星形胶质细胞, 11β-羟基类固醇脱氢酶1型, 肥胖相关性认知损害, 炎症, 内质网应激

Abstract: Objective To investigate the molecular mechanism by which inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) alleviates palmitic acid-induced reactive astrocyte activation. Methods Primary astrocytes were isolated from the hippocampal tissue of neonatal rats and cultured in vitro. The cells were divided into a control group, a palmitic acid group, a palmitic acid + BVT.2733 treatment group, and a palmitic acid-treated 11β-HSD1 knockout cell group. Transmission electron microscopy, immunofluorescence, reverse transcription quantitative real-time PCR (RT-qPCR), and Western blot were used to evaluate cellular ultrastructure, morphology, and the expression levels of relevant genes and proteins. Transcriptome sequencing and bioinformatics analysis were performed to screen for differentially expressed genes and pathways. Results Palmitic acid induced the conversion of astrocytes into the A1 reactive phenotype, and activated the nuclear factor Kappa-B (NF-κB) mediated inflammatory signaling pathway(P<0.05). Knockout of the 11β-HSD1 gene or treatment with BVT.2733 significantly ameliorated palmitic acid-induced ultrastructural damage, inhibited A1 phenotype conversion, and attenuated the inflammatory response(P<0.05). Transcriptome sequencing and gene set enrichment analysis (GSEA) suggested that the NF-κB-mediated signaling pathway may serve as a key downstream pathway by which 11β-HSD1 regulated astrocyte function. Conclusions Inhibition of 11β-HSD1 can alleviate ultrastructural damage, inhibit A1 conversion, and attenuate the inflammatory response in astrocytes, which may serve as a potential target for the intervention of obesity-associated cognitive dysfunction.

Key words: astrocytes, 11β-hydroxysteroid dehydrogenase type 1, obesity-related cognitive impairment, inflammation, endoplasmic reticulum stress

中图分类号:

韦丽琴, 秦丽, 李国超, 庄梦萍, 张钰旻, 刘娟. 抑制11β-HSD1缓解棕榈酸诱导的反应性星形胶质细胞活化的机制研究[J]. 实用老年医学, 2026, 40(10): 997-1005.

WEI Liqin, QIN Li, LI Guochao, ZHUANG Mengping, ZHANG Yumin, LIU Juan. Mechanism of 11β-HSD1 inhibition in alleviating palmitic acid-induced reactive astrocyte activation[J]. Practical Geriatrics, 2026, 40(10): 997-1005.

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