Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression

SUN Zijin; WANG Kai; ZHANG Haojia; SONG Linjing; WANG Zhaoyi; XU Wenxiu; JI Jing; SHAN Yonglin; SHI Qianqian; WANG Xueqian; CHENG Fafeng; WANG Qingguo

doi:10.13422/j.cnki.syfjx.20260125

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Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression

更新时间：2026-03-19

- Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 8, Pages: 54-63(2026)
- 作者机构：
  
  1.北京中医药大学中医学院，北京 102446
  2.北京中医药大学第一临床医学院，北京 100700
  3.康复大学生命科学与健康学院，山东青岛 266113
  4.安徽中医药大学中西医结合学院，合肥 230038
  5.河北省沧州中西医结合医院，河北沧州 061001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20260125
  CLC： R256;R259;R285
- Received：19 August 2025，
  
  Revised：2025-12-09，
  
  Accepted：10 December 2025，
  
  Online First：12 December 2025，
  
  Published：20 April 2026
- 稿件说明：
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孙资金,王凯,张浩嘉等.黄连解毒汤对小鼠局部脑缺血再灌损伤作用及其少突胶质细胞相关基因表达的影响[J].中国实验方剂学杂志,2026,32(08):54-63.

SUN Zijin,WANG Kai,ZHANG Haojia,et al.Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(08):54-63.
孙资金,王凯,张浩嘉等.黄连解毒汤对小鼠局部脑缺血再灌损伤作用及其少突胶质细胞相关基因表达的影响[J].中国实验方剂学杂志,2026,32(08):54-63. DOI： 10.13422/j.cnki.syfjx.20260125.

SUN Zijin,WANG Kai,ZHANG Haojia,et al.Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(08):54-63. DOI： 10.13422/j.cnki.syfjx.20260125.

摘要

目的

该研究旨在评估黄连解毒汤对大脑中动脉闭塞（MCAO）小鼠模型中脑梗死损伤的治疗效果，并探讨其对少突胶质细胞的作用机制，特别是在髓鞘修复中的潜力。

方法

该研究采用多种实验手段评估脑缺血损伤及药物干预效果。采用激光散斑成像检测脑血流变化，2，3，5-三苯基四唑氯化物（TTC）染色测量梗死体积，并依据Zea-Longa标准进行神经功能评分。脑组织经常规石蜡包埋后行苏木素-伊红（HE）和尼氏（Nissl）染色，用于观察组织结构和神经元损伤情况。动物分为假手术组（

=24）、模型组（

=24）、黄连解毒汤组（

=24）和银杏叶提取物组（

=18）。适应饲养1周后开始灌胃给药：假手术组和模型组给予生理盐水；黄连解毒汤组按1.82 g·kg

-1

给药；银杏叶提取物组配制成2.16 g·L

-1

溶液后按0.432 g·kg

-1

给药。各组连续给药5 d，给药体积为0.2 mL·（10 g）

-1

·d

-1

。第6天末次给药后建立MCAO模型。采用单细胞RNA测序分析脑组织细胞组成与少突胶质细胞亚群变化。经均匀流形逼近与投影（UMAP）降维和无监督聚类识别不同亚群，并分析其标志基因表达。进一步使用IPA进行通路富集和因果推断。最后通过实时荧光定量聚合酶链式反应（Real-time PCR）验证髓鞘相关基因的mRNA表达变化。

结果

与假手术组比较，模型组表现出神经功能评分显著上调（

0.01），血流量显著受损（

0.01），脑梗死面积显著增大（

0.01），且出现皮质结构排列失序、胞体空泡化加剧及Nissl小体增多的病理改变；与模型组比较，黄连解毒汤组与银杏叶提取物组则显示出神经功能评分显著下降（

0.01），血流量水平明显回升（

0.01），脑梗死面积显著减小（

0.01），同时皮质结构紊乱得到改善，胞体空泡化程度减轻，Nissl小体数量亦有所减少。单细胞数据显示，少突胶质细胞中存在髓鞘相关型少突胶质细胞（Mye Oil）的亚群，该亚群与髓鞘生成密切相关。与假手术组比较，模型组中Mye Oil数目减少；与模型组比较，黄连解毒汤组Mye Oil数目增多。并该亚群通过OLIG1、OLIG2、NKX2-2、SOX10等转录因子，促进MOG、MBP、MAG等髓鞘生成基因的表达，进而调控髓鞘生成，恢复认知，对急性脑梗死产生治疗效果。与假手术组比较，模型组小鼠OLI

G1、OLIG2、NKX2-2、SOX10 mRNA表达水平显著下调（

0.01），且MOG、MBP、MAG等髓鞘生成相关mRNA表达水平亦显著下调（

0.01）；而与模型组比较，黄连解毒汤组与银杏叶提取物组的OLIG1、OLIG2、NKX2-2、SOX10 mRNA表达水平显著上调（

0.01），且MOG、MBP、MAG等髓鞘生成相关mRNA表达水平亦显著上调（

0.01）。

结论

黄连解毒汤可通过调节OLIG1/2-NKX2-2-SOX10信号通路，促进Mye Oil进行髓鞘生成，对急性脑梗死产生治疗效果。

Abstract

Objective

To evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair.

Methods

Multiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （

=24）， model group （

=24）， Huanglian Jiedutang group （

=24）， and Ginkgo biloba extract （GBE） group （

=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg

-1

， and the GBE group was administered 0.432 g·kg

-1

after preparation as a 2.16 g·L

-1

solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）

¹·d

¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition

and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes.

Results

Compared with the sham group， the model group showed significantly increased neurological function scores （

0.01）， significantly impaired blood flow （

0.01）， significantly enlarged cerebral infarct area （

0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （

0.01）， markedly restored blood flow levels （

0.01）， significantly reduced cerebral infarct area （

0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significa

ntly downregulated in the model group （

0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （

0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （

0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （

0.01）.

Conclusion

Huanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

关键词

Keywords

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