| 桃红四物汤通过抑制NLRP3/caspase-1介导的小胶质细胞焦亡减轻神经损伤的机制研究 |
| 投稿时间：2025-02-04 修订日期：2025-02-09 点此下载全文 |
| 引用本文：陈新茹,王慧芳,周娴,陈梦圆,张艳艳,季兆洁.桃红四物汤通过抑制NLRP3/caspase-1介导的小胶质细胞焦亡减轻神经损伤的机制研究[J].医学研究杂志,2025,54(6):57-63 |
| DOI：
10.11969/j.issn.1673-548X.2025.06.011 |
| 摘要点击次数: 17 |
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| 基金项目:国家自然科学基金青年科学基金资助项目(82074152,82304912)；安徽省高校自然科学研究重点项目(2023AH050744) |
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| 中文摘要:目的 探讨在氧糖剥夺再灌注(oxygen-glucose deprivation/reperfusion, OGD/R)损伤下,桃红四物汤在小胶质细胞焦亡介导的PC12细胞损伤中的作用机制。方法 将PC12与BV2细胞共培养,采用氧糖剥夺4～6h,复糖复氧24h,构建体外OGD/R模型。实验分为对照组(PC12, PC12+BV2)、OGD/R组(PC12, PC12+BV2)、OGD/R+10%桃红四物汤含药血清组(PC12, PC12+BV2),通过CCK-8和流式细胞术评估PC12细胞的损伤程度。采用BV2细胞单独进行实验,分为对照组、OGD/R组和OGD/R+桃红四物汤含药血清(5%、10%、15%)组,经相同方式造模给药后,通过免疫印迹(Western blot)法检测细胞焦亡蛋白胱天蛋白酶-1(cysteine aspartic acid specific protease-1,caspase-1)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD, ASC)、GSDM家族蛋白(gasdermin D,GSDMD)、白介素 1β(interleukin-1β,IL-1β)、白介素18(interleukin-18,IL-18)和Nod样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎性小体相关蛋白的表达水平。结果 在BV2细胞存在条件下,桃红四物汤能够进一步恢复OGD/R损伤后PC12细胞的形态,增强细胞活力(P＜0.05),减少细胞凋亡(P＜0.05),并能够降低OGD/R诱导的BV2细胞焦亡蛋白(caspase-1、ASC、GSDMD、IL-1β、IL-18)的表达水平(P＜0.05)。相反,桃红四物汤对BV2细胞焦亡蛋白和NLRP3炎性小体的抑制作用被NLRP3激动剂逆转 (P＜0.05)。结论 桃红四物汤通过NLRP3/caspase-1途径抑制小胶质细胞焦亡,减轻OGD/R诱导的PC12细胞损伤。 |
| 中文关键词:桃红四物汤 小胶质细胞 焦亡 NLRP3炎性小体 氧糖剥夺再灌注损伤 |
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| Taohong Siwu Decoction Alleviates Neural Injury by Inhibiting NLRP3/caspase-1-Mediated Pyroptosis of Microglia. |
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| Abstract:Objective To investigate the role of Taohong Siwu Decoction(THSWD) in microglia pyroptosis mediated neuronal injury in PC12 under oxygen-glucose deprivation/reperfusion (OGD/R) and related mechanisms. Methods PC12 and BV2 cells were co-cultured using the OGD/R model to simulate ischemia-reperfusion injury of in vitro. The experiment was grouped as follows:control (PC12, PC12+BV2), OGD/R group (PC12, PC12+BV2), and OGD/R+10% THSWD-containing serum group (PC12, PC12+BV2). Oxygen and glucose was restored for 24h after 4-6h of deprivation. The severity of damage to PC12 cells was evaluated by cell counting kit-8 (CCK-8) and flow cytometry. BV2 cells were used for the experiments and were divided into control, OGD/R and OGD/R+THSWD-containing serum (5%, 10%, 15%) groups, which were moulded and administered in the same way, and cell pyroptosis proteins proteinscysteinyl aspartate specific proteinase-1 (caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D (GSDMD), interleukin-1β (IL-1β), interleukin-18 (IL-18) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-associated proteins were detected by Western blot. Results In the presence of BV2 cells, THSWD was able to further restore the morphology, increase cell viability (P＜0.05) and reduce apoptosis of PC12 cells after OGD/R injury (P＜0.05). In addition, THSWD was able to reduce the expression of OGD/R-induced pyroptosis proteins (caspase-1, ASC, GSDMD, IL-1β, IL-18) in BV2 microglia cells (P＜0.05). In contrast, the inhibitory effects of THSWD on BV2 cells pyroptosis proteins and NLRP3 inflammasome were reversed by NLRP3/caspase-1 agonist (P＜0.05). Conclusion THSWD protects PC12 cells against OGD/R injury via inhibiting microglia pyroptosis mediated by the NLRP3/caspase-1 pathway. |
| keywords:Taohong Siwu decoction Microglia Pyroptosis NLRP3 inflammasome Oxygen glucose deprivation/reperfusion |
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