The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 6: 999 - 1007

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.06.012

Chronic Disease Control

Study on the role and mechanism of inhibiting miR-203a-3p expression in collateral circulation reconstruction in rats with cerebral ischemia-reperfusion injury model

  • Mengxue ZANG ,
  • Tianqi HAN ,
  • Ying DAI ,
  • Haiyan CHEN ,
  • Lizhi PENG ,
  • Yongming JIANG ,
  • Guixin YANG ,
  • Hui LIANG ,
  • Xuebin LI ,
  • Jianmin HUANG
Expand
  • 1.Graduate School of Youjiang Medical University for Nationalities，Baise 533000，Guangxi，China
    2.Department of Neurology，the Affiliated Hospital of Youjiang Medical University for Nationalities，Baise 533000，Guangxi，China

Received date: 2025-12-09

  Revised date: 2026-01-14

  Accepted date: 2026-01-15

  Online published: 2026-03-26

Fold

Abstract

Objective To investigate the effect of lateral ventricle injection of miR-203a-3p antagonist（antagomir）on collateral circulation recanalization and its underlying mechanisms in rats with cerebral ischemia-reperfusion injury（CIRI）. Methods Sprague-Dawley rats were randomly allocated into four experimental groups： the sham group， the model group， the antagomiR-NC group， and the antagomiR-203a-3p group. CIRI was induced in the model， antagomiR-NC， and antagomiR-203a-3p groups using the thread embolization technique to establish the CIRI model. Twenty-four hours prior to CIRI induction， rats in the antagomiR-NC and antagomiR-203a-3p groups received a stereotaxic injection of antagomiR-NC and miR-203a-3p antagomir， respectively， into the lateral ventricle. Rats in the sham and model groups were administered an equivalent volume of sterile saline via the same route and at the same time point.Behavioral assessments were conducted using the Zea-Longa scoring system. Cerebral infarction volume was measured using TTC staining. Collateral circulation status and microcirculatory blood perfusion （MBPU） in the rat cerebral cortex were monitored using laser speckle imaging. Cortical pathological morphology was observed through hematoxylin and eosin staining. RT-qPCR was employed to analyze the expression of miR-203a-3p， PIK3CA， PI3K， AKT， and Survivin mRNA in rat brain tissue. Western blotting was employed to detect the expression of PIK3CA， p-PI3K， PI3K， p-AKT， AKT and Survivin proteins. Results In comparison to the model group and the antagomiR-NC group， rats in the miR-203a-3p group demonstrated significantly reduced neurological deficit scores， notably decreased cerebral infarct volumes，substantially more collateral circulation anastomoses could be seen， and increased MBPU in the cerebral cortex. Pathological damage in cortical regions was mitigated， with miR-203a-3p mRNA expression levels markedly decreased， while mRNA expression levels of PIK3CA， PI3K， Akt， and Survivin were significantly elevated. Correspondingly， protein expression levels of PIK3CA， p-PI3K/PI3K、p-AKT/AKT and Survivin were markedly increased. Conclusions The inhibition of miR-203a-3p expression enhances cortical MBPU and the opening of collateral circulation in rats with CIRI， thereby reducing pathological damage and improving neurological function. This mechanism may be associated with the activation of the PIK3CA/PI3K/AKT/Survivin signaling pathway by the miR-203a-3p antagomir， which facilitates the reconstruction of collateral circulation.

Key words： miR-203a-3p; PIK3CA/PI3K/Akt/Survivin signaling pathway; cerebral ischemia reperfusion injury; collateral circulation; rats

Cite this article

Mengxue ZANG , Tianqi HAN , Ying DAI , Haiyan CHEN , Lizhi PENG , Yongming JIANG , Guixin YANG , Hui LIANG , Xuebin LI , Jianmin HUANG . Study on the role and mechanism of inhibiting miR-203a-3p expression in collateral circulation reconstruction in rats with cerebral ischemia-reperfusion injury model[J]. The Journal of Practical Medicine, 2026 , 42(6) : 999 -1007 . DOI: 10.3969/j.issn.1006-5725.2026.06.012

References

[1] MAIDA C D， NORRITO R L， RIZZICA S， et al. Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes： Background and Therapeutic Approaches ［J］. Int J Mol Sci， 2024，25（12）：6297. doi：10.3390/ijms25126297 .
[2] OH M， LEE M. Clinical Implications of Prominent Cortical Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke Patients Treated with Recanalization Therapy ［J］. Brain Sci， 2022，12（2）：184. doi：10.3390/brainsci12020184 .
[3] LI X， WANG F， ZHAO Z， et al. A SCANO Nomogram for Individualized Prediction of the Probability of 1-Year Unfavorable Outcomes in Chinese Acute Ischemic Stroke Patients ［J］.Front Neurol， 2020，11：531. doi：10.3389/fneur.2020.00531 .
[4] LI X， LI S， MA C， et al. Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia ［J］. Drug Deliv， 2022，29（1）：1282-1298. doi：10.1080/10717544.2022.2064564 .
[5] HE Q， WANG Y， FANG C， et al. Advancing stroke therapy： A deep dive into early phase of ischemic stroke and recanalization ［J］. CNS Neurosci Ther， 2024，30（2）：e14634. doi：10.1111/cns.14634 .
[6] AL-AJLAN F S， ALKHIRI A， ALAMRI A F， et al. Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke： A Systematic Review and Meta‐Analysis ［J］. Ann Neurol， 2024，96（3）：582-590. doi：10.1002/ana.27007 .
[7] 姜浩， 程凯理， 陈柳. 血清血小板反应蛋白-1联合阿尔伯塔中风项目早期CT评分对大动脉闭塞性急性脑梗死患者预后的评估价值 ［J］. 实用医学杂志， 2025，41（16）：2561-2567. doi：10.3969/j.issn.1006-5725.2025.16.018 .
[8] ZHANG X， DUAN G， ZHANG H， et al. Safety and effectiveness assessment of endovascular recanalization fornon‐acute middle cerebral artery occlusion ［J］.CNS Neurosci Ther， 2024，30（3）：e14426. doi：10.1111/cns.14426 .
[9] MAGUIDA G， SHUAIB A. Collateral Circulation in Ischemic Stroke： An Updated Review ［J］.J Stroke， 2023，25（2）：179-198. doi：10.5853/jos.2022.02936 .
[10] HUANG J， LI X， ZHAO J， et al. Association of BIRC5 Gene Polymorphism with the Collateral Circulation and Severity of Large Artery Atherosclerotic Stroke ［J］. Int J Clin Pract， 2022，2022（1）：9177545. doi：10.1155/2022/9177545 .
[11] 李雪斌， 黄建敏， 云艳芳， 等.生存素抑制剂YM155对脑梗死大鼠微血管密度及血管新生相关基因表达的影响 ［J］. 实用医学杂志， 2022， 38 （8）：946-951. doi：10.3969/j.issn.1006-5725.2022.08.007 .
[12] 李雪斌， 黄建敏， 陈海燕， 等. 过表达BIRC5基因对氧糖剥夺/复氧诱导的脑微血管内皮细胞活性及VEGF表达的影响［J］. 右江民族医学院学报， 2024，46（1）：1-7. doi：10.3969/j.issn. 1001-5817.2024.01.001 .
[13] 朱腾腾. miR-203a-3p通过PIK3CA/PI3K/Akt通路调控PASMCs的增殖和迁移在PAH中的机制研究 ［D］. 长沙：中南大学， 2023. doi：10.27661/d.cnki.gzhnu.2023.000221 .
[14] HU Z， ZHUO L， LI Y， et al. MicroRNA?203a?3p suppresses endothelial cell proliferation and invasion， and promotes apoptosis in hemangioma by inactivating the VEGF?mediated PI3K/AKT pathway ［J］. Exp Ther Med， 2022，24（5）：644. doi：10.3892/etm. 2022.11581 .
[15] 胡琳， 杨艳娟， 李洁滢， 等. 红景天苷通过激活PI3K/Akt和抑制NF ? κ B信号通路改善川崎病冠状动脉损伤 ［J］. 实用医学杂志， 2022， 38 （21）： 2657-2662. doi：10.3969/j.issn.1006-5725.2022.21.005 .
[16] GREITHER T， KOSER F， HOLZHAUSEN H， et al. MiR-155-5p and MiR-203a-3p Are Prognostic Factors in Soft Tissue Sarcoma ［J］. Cancers （Basel）， 2020，12（8）：2254. doi：10.3390/cancers12082254 .
[17] ENTEZARI M， SOLTANI B M， SADEGHIZADEH M. MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways ［J］. Sci Rep， 2024，14（1）：4715. doi：10.1038/s41598-024-52940-5 .
[18] ZHUO L， HU Z， CHANG J， et al. MicroRNA?203a?3p improves bleomycin and pingyangmycin sensitivity by inactivating the PI3K/AKT pathway in hemangioma ［J］. Exp Ther Med， 2024，27（2）. doi：10.3892/etm.2024.12369 .
[19] 袁柳媚， 卢小叶， 云夏， 等. 线栓法制备大鼠大脑中动脉闭塞脑缺血模型的体会 ［J］. 中国医药科学， 2022，12（2）： 7-10. doi：10.3969/j.issn.2095-0616.2022.02.003 .
[20] LI Q， ZHANG H， LIU X. Didymin Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the PPAR Signaling Pathway ［J］. Yonsei Med J， 2022，63（10）：956. doi：10.3349/ymj. 2022.0040 .
[21] WANG L， SHI Q， XUE Y， et al. Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic： A propensity score-matched analysis ［J］.Medicine （Baltimore）， 2024，103（21）：e38254. doi：10.1097/MD.0000000000038254 .
[22] YUN S W， KIM W Y， LEE J B. Correlation between Serum Erythropoietin and Cerebral Collateral Flow in Acute Ischemic Stroke Patient ［J］.Korean J Fam Med， 2023，44（1）：53-57. doi：10.4082/kjfm.22.0117 .
[23] 陈英道， 李海宁， 张岐平， 等. 脑侧支循环对急性脑梗死患者机械取栓术后疗效及预后的影响 ［J］. 实用医学杂志， 2021， 37 （12）： 1563-1568. doi：10.3969/j.issn.1006-5725.2021. 12.011 .
[24] CAI W， LIU S， LIU Z， et al. Downregulation of lung miR-203a-3p expression by high-altitude hypoxia enhances VEGF/Notch signaling ［J］. Aging （Albany NY）， 2020， 12（5）： 4247-4267. doi：10.18632/aging.102878 .
[25] JEON Y S， KIM H J， ROH H G， et al. Impact of Collateral Circulation on Futile Endovascular Thrombectomy in Acute Anterior Circulation Ischemic Stroke ［J］. J Korean Neurosurg Soc， 2024，67（1）：31-41. doi：10.3340/jkns.2023.0139 .
[26] LEE J M， SHIN Y J， BYOUNG-SOO S， et al. A case series of acute ischemic strokes with contralateral perfusion time delay on brain computed tomography ［J］.Medicine （Baltimore）， 2023，102（19）：e33790. doi：10.1097/MD.0000000000033790 .
[27] HAN G， LI D， WANG J， et al. Adaptive window space direction laser speckle contrast imaging to improve vascular visualization ［J］. Biomed Opt Express， 2023， 14（6）： 3086-3099. doi：10.1364/BOE.488054 .
[28] KIM Y， CHOI W J， OH J， et al. Compact Smartphone-Based Laser Speckle Contrast Imaging Endoscope Device for Point-of-Care Blood Flow Monitoring ［J］. Biosensors （Basel）， 2022，12（6）：398. doi：10.3390/bios12060398 .
[29] LI K， GAO Z， GUO Y， et al. Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis ［J］. Exp Brain Res， 2024， 242（4）： 869-878. doi：10.1007/s00221-024-06778-y .
[30] YANG X， LI X， LIN Q， et al. Up-regulation of microRNA-203 inhibits myocardial fibrosis and oxidative stress in mice with diabetic cardiomyopathy through the inhibition of PI3K/Akt signaling pathway via PIK3CA ［J］.Gene， 2019，715：143995. doi：10.1016/j.gene.2019.143995 .
[31] YU L， FU J， YU N， et al. Long noncoding RNA MALAT1 participates in the pathological angiogenesis of diabetic retinopathy in an oxygen-induced retinopathy mouse model by sponging miR-203a-3p ［J］. Can J Physiol Pharmacol， 2020，98（4）：219-227. doi：10.1139/cjpp-2019-0489 .
[32] XU Y， TAN X， WANG D， et al. Elevated survivin expression in peripheral blood mononuclear cells is central to collateral formation in coronary chronic total occlusion ［J］. Int J Mol Med， 2015，35（6）：1501-1510. doi：10.3892/ijmm.2015.2154 .
[33] MA J， MA Y， SHUAIB A， et al. Improved collateral flow and reduced damage after remote ischemic perconditioning during distal middle cerebral artery occlusion in aged rats ［J］. Sci Rep， 2020，10（1）：12392. doi：10.1038/s41598-020-69122-8 .
[34] LV H， LIU X， CHEN W， et al. Yangxue Jiedu Fang Ameliorates Psoriasis by Regulating Vascular Regression via Survivin/PI3K/Akt Pathway ［J］. J Immunol Res， 2021，2021：1-18. doi：10.1155/2021/4678087 .
[35] CANDIDO S， SALEMI R， PICCININ S， et al. The PIK3CA H1047R Mutation Confers Resistance to BRAF and MEK Inhibitors in A375 Melanoma Cells through the Cross-Activation of MAPK and PI3K-Akt Pathways ［J］.Pharmaceutics， 2022，14（3）：590. doi：10.3390/pharmaceutics14030590 .
[36] LI Q， TANG Y， ZUO J， et al. CENP-H as a new prognostic biomarker for tumors： A real-world literature review ［J］. Front Oncol， 2025，15：1521988. doi：10.3389/fonc.2025.1521988 .
Options
Outlines

/

〈 〉