Mechanisms of Propofol in Alleviating Neuropathic Pain by Inhibiting Microglial Pyroptosis in Spinal Cord Through the KDM3A/WNT5A Axis

IF 2.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI:10.1002/jbt.70498

Sun-hui Xia, Di Zhou, Yuqiu Zhang, Jing Jiao, Changhong Miao

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Abstract

Propofol is a short-acting intravenous anesthetic commonly used for induction and maintenance of general anesthesia and sedation during medical procedures. This study aimed to explore the mechanism of propofol on microglial pyroptosis in spinal cord in neuropathic pain (NP). A chronic constriction injury (CCI) model of NP was established in rats. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in rats. The tissue pathology was observed. The expression of NLR family pyrin domain containing 3 (NLRP3) and Iba1 was measured. Microglial cells (BV2) were cultured and treated with lipopolysaccharide (LPS). The cell model was treated with propofol. The levels of lysine demethylase 3A (KDM3A)/H3 dimethylation at lysine 9 (H3K9me2)/Wnt family member 5A (WNT5A) in the tissue and cells were measured. The enrichment of KDM3A and H3K9me2 in the WNT5A promoter region was analyzed. KDM3A and WNT5A were upregulated in CCI. Propofol treatment reduced KDM3A and WNT5A expression, increased PWMT and PWTL, alleviated inflammation, and inhibited microglial pyroptosis in spinal cord. KDM3A promoted WNT5A expression by inhibiting H3K9me2. Overexpression of KDM3A or WNT5A partially reversed the inhibitory effect of propofol on pyroptosis. In conclusion, propofol inhibits microglial pyroptosis in spinal cord and alleviates NP through the KDM3A/WNT5A pathway.

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异丙酚通过KDM3A/WNT5A轴抑制脊髓小胶质细胞焦亡减轻神经性疼痛的机制

异丙酚是一种短效静脉麻醉药，通常用于诱导和维持全身麻醉和医疗过程中的镇静。本研究旨在探讨异丙酚对神经性疼痛（NP）脊髓小胶质细胞焦亡的作用机制。建立大鼠NP慢性缩窄性损伤模型。测定了大鼠足退缩机械阈值（PWMT）和足退缩热潜伏期（PWTL）。观察组织病理变化。检测NLR家族pyrin domain containing 3 （NLRP3）和Iba1的表达。培养小胶质细胞（BV2）并用脂多糖（LPS）处理。用异丙酚处理细胞模型。测定组织和细胞中赖氨酸9 (H3K9me2)/Wnt家族成员5A （WNT5A）位点赖氨酸去甲基化酶3A (KDM3A)/H3二甲基化水平。分析了WNT5A启动子区KDM3A和H3K9me2的富集情况。KDM3A和WNT5A在CCI中表达上调。异丙酚治疗降低KDM3A和WNT5A表达，增加PWMT和PWTL，减轻炎症，抑制脊髓小胶质细胞焦亡。KDM3A通过抑制H3K9me2促进WNT5A的表达。KDM3A或WNT5A的过表达部分逆转了异丙酚对焦亡的抑制作用。综上所述，异丙酚通过KDM3A/WNT5A通路抑制脊髓小胶质细胞焦亡，减轻NP。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.