Mechanism study of miR-379-5p in improving cerebral ischemia-reperfusion injury in rats

WANG Ming-yuan; ZHANG Ya-jie; SHA Jing; DANG Hui; LI Hong-yan

doi:10.11659/jjssx.06E025148

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Mechanism study of miR-379-5p in improving cerebral ischemia-reperfusion injury in rats

Basic Research | 更新时间：2026-04-20

- Mechanism study of miR-379-5p in improving cerebral ischemia-reperfusion injury in rats
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 4, Pages: 321-327(2026)
- 作者机构：
  
  新疆维吾尔自治区人民医院神经内科，新疆乌鲁木齐 830001
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.06E025148
  CLC： R743.3
- Received：27 June 2025，
  
  Published：25 April 2026
- 稿件说明：
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王明远,张娅洁,沙晶等.miR-379-5p改善大鼠脑缺血再灌注损伤的机制研究[J].局解手术学杂志,2026,35(04):321-327.

WANG Ming-yuan,ZHANG Ya-jie,SHA Jing,et al.Mechanism study of miR-379-5p in improving cerebral ischemia-reperfusion injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(04):321-327.
王明远,张娅洁,沙晶等.miR-379-5p改善大鼠脑缺血再灌注损伤的机制研究[J].局解手术学杂志,2026,35(04):321-327. DOI： 10.11659/jjssx.06E025148.

WANG Ming-yuan,ZHANG Ya-jie,SHA Jing,et al.Mechanism study of miR-379-5p in improving cerebral ischemia-reperfusion injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(04):321-327. DOI： 10.11659/jjssx.06E025148.

摘要

目的

探究miR-379-5p对大鼠脑缺血再灌注损伤（CIRI）的影响及其作用机制。

方法

采用短暂性阻断大脑中动脉的方法构建CIRI大鼠模型，并随机分为模型组、miR-379-5p激动剂组（侧脑室注射miR-379-5p激动剂）、miR-379-5p拮抗剂组（侧脑室注射miR-379-5p拮抗剂）、消皮素D（GSDMD）抑制剂组（侧脑室注射80 nmol necrosulfonamide），另将仅暴露颈内动脉和颈外动脉的大鼠设为假手术组。采用改良神经功能缺损评分（mNSS）评估各组大鼠神经功能缺损程度，2

5-氯化三苯基四氮唑（TTC）染色和苏木精-伊红（HE）染色观察各组大鼠脑组织梗死情况及形态结构变化，TUNEL染色检测各组大鼠脑组织神经元凋亡情况，RT-qPCR检测各组大鼠脑组织中miR-379-5p表达水平，免疫荧光染色、Western blot检测各组大鼠脑组织中GSDMD荧光表达及NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、前体半胱天冬酶-1（pro-Caspase-1）、GSDMD、GSDMD蛋白N端片段（GSDMD-N）蛋白表达水平。

结果

与模型组比较，miR-379-5p激动剂组、GSDMD抑制剂组大鼠mNSS评分降低，脑组织梗死面积减少，脑组织皮质层神经元排列紊乱、细胞肿胀、空泡样等病变现象显著改善，神经元凋亡指数降低，miR-379-5p表达水平上调，GSDMD平均荧光密度及NLRP3、ASC、pro-Caspase-1、GSDMD、GSDMD-N蛋白表达水平下调，差异均有统计学意义（

0.05）；而与模型组比较，miR-379-5p拮抗剂组大鼠mNSS评分升高，脑组织梗死面积增加，神经元排列紊乱、细胞肿胀及空泡样等病变现象加重，神经元凋亡指数升高，miR-379-5p表达水平下调，GSDMD平均荧光密度及NLRP3、ASC、pro-Caspase-1、GSDMD、GSDMD-N蛋白表达水平进一步上调，差异均有统计学意义（

0.05）。

结论

上调miR-379-5p表达对CIRI大鼠具有保护作用，其作用机制可能与抑制GSDMD介导的细胞焦亡有关。

Abstract

Objective

To investigate the effect of miR-379-5p on cerebral ischemia-reperfusion injury （CIRI） in rats and its underlying mechanism.

Methods

The CIRI rat model was established by transiently blocking the middle cerebral artery. The rats were randomly divided into the model group， the miR-379-5p agonist group （injection of miR-379-5p agonist into the lateral ventricle）， the miR-379-5p antagonist group （injection of miR-379-5p antagonist into the lateral ventricle）， the gasdermin D （GSDMD） inhibitor group （injection of 80 nmol necrosulfonamide into the lateral ventricle）. In addition， rats with only the internal and external carotid arteries exposed were designated as the sham-operated group. The modified neurological severity score （mNSS） was used to evaluate the degree of neurological deficits of rats in each group. 2，3，5-triphenyltetrazolium chloride （TTC） staining and hematoxylin-eosin （HE） staining were used to observe the cerebral infarction and morphological changes in the brain tissues of rats in each group. TUNEL staining was used to detect the neuronal apoptosis in the brain tissues of rats in each group. RT-qPCR was used to detect the expression level of miR-379-5p in the brain tissues of rats in each group. Immunofluorescence staining and Western blot were used to detect the fluorescence expression of GSDMD and the protein expression levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， pro-Caspase-1， GSDMD and N-terminal active fragment of GSDMD （GSDMD-N） in the brain tissues of rats in each group.

Results

Compared with the model group， the mNSS scores of rats in the miR-379-5p agonist group and the GSDMD inhibitor group were decreased， the infarct area of brain tissue was reduced， the disordered arrangement of neurons， cell swelling， and vacuolation in the cortical brain tissue were significantly improved， the neuronal apoptosis index was decreased， the miR-379-5p expression level was upregulated， the mean fluorescence density of GSDMD and the protein expression levels of NLRP3， ASC， pro-Caspase-1， GSDMD， and GSDMD-N were downregulated， and all these differences were statistically significant （

05）. Compared with the model group， the mNSS score of rats in the miR-379-5p antagonist group was increased， the infarct area of brain tissue was increased， the disordered arrangement of neurons， cell swelling and vacuolation were aggravated， the neuronal apoptosis index was increased， the miR-379-5p expression level was downregulated， the mean fluorescence density of GSDMD and the protein expression levels of NLRP3， ASC， pro-Caspase-1， GSDMD， GSDMD-N were further upregulated， and all these differences were statistically significant （

0.05）.

Conclusion

Upregulation of miR-379-5p expression has a protective effect on CIRI rats， and its mechanism of action may be related to the inhibition of GSDMD-mediated pyroptosis.

关键词

Keywords

references

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