Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (2): 316-325.DOI: 10.19852/j.cnki.jtcm.2026.02.005
• Original Articles • Previous Articles Next Articles
Acupuncture inhibits astrocytic hyperactivation via the p38 mitogen-activated protein kinase/mitogen- and stress-activated protein kinase 1 signaling pathway in cerebral ischemia-reperfusion injury
ZHUANG Zifeng1, WO Choying1, CHEN Hongling1, XIE Hailiang2, ZHAO Canghuan2, ZHANG Di1(
), QING Peng2()
- 1
College of Traditional Chinese Medicine ,Jinan University Guangzhou 510632, China
2Department of Acupuncture ,the First Affiliated Hospital of Jinan University Guangzhou 510630, China
-
Received:2025-06-11Accepted:2025-11-10Online:2026-04-15Published:2026-04-04 -
Contact:ZHANG Di, College of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China. dizhang0915@jnu.edu.cn; QING Peng, Department of Acupuncture, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China. qingpeng5602@163.com; Telephone: +86-15521245050 -
Supported by:Guangzhou Basic and Applied Basic Research Foundation: Mechanistic Investigation of Ziwu Liuzhu Acupuncture for Insomnia Based on the Heat Shock Protein 90/Stimulator of Interferon Genes-nuclear Factor Kappa B Immune Pathway and Its Regulation of Sleep-Wake Rhythms(2025A03J3400);Guangdong Basic and Applied Basic Research Foundation: Danggui Sini Decoction Promotes Damaged Nerve Repair and Treats Sciatica by Inhibiting Secreted Phosphoprotein 1/Cluster of Differentiation 44-Mediated Macrophage-Schwann Cell Crosstalk(2025A1515011267);Guangzhou Doctoral Start-up Program: Danggui Sini Decoction Regulates Angiopoietin-like 4/Syndecan-4-mediated Neurovascular Coupling to Promote Injured Nerve Repair for the Treatment of Sciatica(2025A04J3397);National Natural Science Foundation of China (Youth Program): Investigation of Danggui Sini Decoction in Improving Neuro-microcirculation and Promoting Nerve Repair for the Treatment of Sciatica Based on Angptl4/Sdc4-mediated Endothelial Cell-Schwann Cell Coupling(82405081);China Postdoctoral Science Foundation Special Funding (Pre-Station): Danggui Sini Decoction Inhibits Peripheral Sensitization and Alleviates Sciatica by Regulating Macrophage-neuron Crosstalk(2023TQ0135);China Postdoctoral Science Foundation General Funding: Danggui Sini Decoction Promotes Damaged Nerve Repair and Treats Sciatica by Modulating Endothelial Cell-schwann Cell Coupling(2024M751136)
Cite this article
ZHUANG Zifeng, WO Choying, CHEN Hongling, XIE Hailiang, ZHAO Canghuan, ZHANG Di, QING Peng. Acupuncture inhibits astrocytic hyperactivation via the p38 mitogen-activated protein kinase/mitogen- and stress-activated protein kinase 1 signaling pathway in cerebral ischemia-reperfusion injury[J]. Journal of Traditional Chinese Medicine, 2026, 46(2): 316-325.
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Figure 1 Transcriptome analysis implicates p38 MAPK/MSK1 signaling in mediating MCAO-induced injury A: volcano plot showing differentially expressed in MCAO; B: KEGG analysis examining differentially expressed genes in MCAO; C: KEGG pathway enrichment analysis highlighting the MAPK signaling pathway; D: enrichment plot of the MAPK signaling pathway identified by gene set enrichment analysis. Sham group: neck incision without filament insertion; MCAO group: ischemic-reperfusion injury without intervention. MCAO: middle cerebral artery occlusion. KEGG: kyoto encyclopedia of genes and genomes; DEGs: differentially expressed genes; GSEA: gene set enrichment analysis; MAPK: mitogen-activated protein kinase; MSK1: mitogen- and stress-activated protein kinase 1.
Figure 1 Transcriptome analysis implicates p38 MAPK/MSK1 signaling in mediating MCAO-induced injury A: volcano plot showing differentially expressed in MCAO; B: KEGG analysis examining differentially expressed genes in MCAO; C: KEGG pathway enrichment analysis highlighting the MAPK signaling pathway; D: enrichment plot of the MAPK signaling pathway identified by gene set enrichment analysis. Sham group: neck incision without filament insertion; MCAO group: ischemic-reperfusion injury without intervention. MCAO: middle cerebral artery occlusion. KEGG: kyoto encyclopedia of genes and genomes; DEGs: differentially expressed genes; GSEA: gene set enrichment analysis; MAPK: mitogen-activated protein kinase; MSK1: mitogen- and stress-activated protein kinase 1.
Figure 2 Single-cell sequencing identified reactive astrocytes in MCAO A: dimensionality reduction of single-cell populations; A1: t-SNE clustering; A2: UMAP clustering; B: volcano plot of differentially expressed genes; C: cell-type proportions; D: pathway enrichment analysis. Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention. MCAO: middle cerebral artery occlusion; t-SNE: t-distributed stochastic neighbor embedding; UMAP: uniform manifold approximation and projection; GFAP: glial fibrillary acidic protein; C3: complement component 3; S100A10: S100 calcium-binding protein A10; Mapk14: mitogen-activated protein kinase 14; IL-6: interleukin-6; IL-1β: interleukin-1 beta; TNF-α: tumor necrosis factor-alpha.
Figure 2 Single-cell sequencing identified reactive astrocytes in MCAO A: dimensionality reduction of single-cell populations; A1: t-SNE clustering; A2: UMAP clustering; B: volcano plot of differentially expressed genes; C: cell-type proportions; D: pathway enrichment analysis. Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention. MCAO: middle cerebral artery occlusion; t-SNE: t-distributed stochastic neighbor embedding; UMAP: uniform manifold approximation and projection; GFAP: glial fibrillary acidic protein; C3: complement component 3; S100A10: S100 calcium-binding protein A10; Mapk14: mitogen-activated protein kinase 14; IL-6: interleukin-6; IL-1β: interleukin-1 beta; TNF-α: tumor necrosis factor-alpha.
Figure 3 Acupuncture improves MCAO-induced brain infarction and fosters neural repair A: TTC staining; B: T2WI; A1, B1: sham group; A2, B2: MCAO group; A3, B3: treat group. C: brain infarct area quantification (n = 3); C1: infarct volume quantified by TTC staining; C2: infarct volume quantified by T2-weighted imaging.Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention; Treat group: MCAO followed by daily acupuncture treatment. Acupuncture was performed at Baihui (GV20) and Dazhui (GV14) using sterilized stainless-steel filiform needles in daily 15-min sessions for 7 d. MCAO: middle cerebral artery occlusion; T2WI: T2-weighted imaging; TTC: 2,3,5-triphenyltetrazolium chloride; ANOVA: analysis of variance. Data are presented as mean ± standard deviation. Behavioral data were analyzed by repeated-measures ANOVA; other data by one-way ANOVA with Tukey’s post hoc test. Compared with the Sham group, aP < 0.05; compared with the MCAO group, bP < 0.05.
Figure 3 Acupuncture improves MCAO-induced brain infarction and fosters neural repair A: TTC staining; B: T2WI; A1, B1: sham group; A2, B2: MCAO group; A3, B3: treat group. C: brain infarct area quantification (n = 3); C1: infarct volume quantified by TTC staining; C2: infarct volume quantified by T2-weighted imaging.Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention; Treat group: MCAO followed by daily acupuncture treatment. Acupuncture was performed at Baihui (GV20) and Dazhui (GV14) using sterilized stainless-steel filiform needles in daily 15-min sessions for 7 d. MCAO: middle cerebral artery occlusion; T2WI: T2-weighted imaging; TTC: 2,3,5-triphenyltetrazolium chloride; ANOVA: analysis of variance. Data are presented as mean ± standard deviation. Behavioral data were analyzed by repeated-measures ANOVA; other data by one-way ANOVA with Tukey’s post hoc test. Compared with the Sham group, aP < 0.05; compared with the MCAO group, bP < 0.05.
Figure 4 Acupuncture modulates reactive astrocyte polarization and improves neurological recovery after ischemia A: Western blot analysis of proteins involved in the p38 MAPK/MSK1 pathway; B1: GFAP; B2: C3; B3: S100A10; B4: MSK1; B5: TNF-α; B6: p-p38 MAPK/p38 MAPK. Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention; treat group: MCAO followed by daily acupuncture treatment. Acupuncture was performed at Baihui (GV20) and Dazhui (GV14) using sterilized stainless-steel filiform needles in daily 15-min sessions for 7 d. GFAP: glial fibrillary acidic protein; C3: complement component 3; S100A10: S100 calcium-binding protein A10; MSK1: mitogen- and stress-activated protein kinase 1; TNF-α: tumor necrosis factor-alpha; p-p38 MAPK: phosphorylated p38 mitogen-activated protein kinase; p38 MAPK: p38 mitogen-activated protein kinase; ANOVA: analysis of variance. The data are presented as mean ± standard deviation (n = 3). Data were analyzed using one-way ANOVA, followed by Tukey’s post hoc test. A P-value < 0.05 was considered statistically significant. Compared with the sham operation group, aP < 0.05; compared with the MCAO group, bP < 0.05.
Figure 4 Acupuncture modulates reactive astrocyte polarization and improves neurological recovery after ischemia A: Western blot analysis of proteins involved in the p38 MAPK/MSK1 pathway; B1: GFAP; B2: C3; B3: S100A10; B4: MSK1; B5: TNF-α; B6: p-p38 MAPK/p38 MAPK. Sham group: neck incision without filament insertion; MCAO group: ischemia-reperfusion injury without intervention; treat group: MCAO followed by daily acupuncture treatment. Acupuncture was performed at Baihui (GV20) and Dazhui (GV14) using sterilized stainless-steel filiform needles in daily 15-min sessions for 7 d. GFAP: glial fibrillary acidic protein; C3: complement component 3; S100A10: S100 calcium-binding protein A10; MSK1: mitogen- and stress-activated protein kinase 1; TNF-α: tumor necrosis factor-alpha; p-p38 MAPK: phosphorylated p38 mitogen-activated protein kinase; p38 MAPK: p38 mitogen-activated protein kinase; ANOVA: analysis of variance. The data are presented as mean ± standard deviation (n = 3). Data were analyzed using one-way ANOVA, followed by Tukey’s post hoc test. A P-value < 0.05 was considered statistically significant. Compared with the sham operation group, aP < 0.05; compared with the MCAO group, bP < 0.05.
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