抑制miR-203a-3p表达在脑缺血再灌注损伤大鼠侧支循环重建中的作用及机制

doi:10.3969/j.issn.1006-5725.2026.06.012

Abstract

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

CLC Number:

R743.32

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.

Figures/Tables 10

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References 36

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组别	n	Longa评分
假手术组	10	0.00 ± 0.00
模型组	10	2.10 ± 0.57^?
antagomiR-NC组	10	2.10 ± 0.86^?
antagomiR-203a-3p组	10	1.10 ± 0.57^{? # &}

组别	n	脑梗死体积/%	大脑皮层MBPU/PU
假手术组	5	0.00 ± 0.00	1 265.63 ± 250.54
模型组	5	26.19 ± 2.68^*	771.13 ± 186.25^*
antagomiR-NC组	5	28.03 ± 2.63^*	710.71 ± 256.16^*
antagomiR-203a-3p组	5	21.49 ± 2.59^{* # &}	1 095.37 ± 185.88^{# &}

组别	miR-203a-3p	PIK3CA	PI3K	AKT	Survivin
假手术组	3.03 ± 0.35	0.49 ± 0.10	0.64 ± 0.09	0.57 ± 0.11	0.59 ± 0.06
模型组	1.20 ± 0.28^?	1.09 ± 0.17^?	1.21 ± 0.19^?	1.20 ± 0.16^?	1.25 ± 0.12^?
antagomiR-NC组	1.19 ± 0.07^?	1.13 ± 0.10^?	1.11 ± 0.08^?	1.12 ± 0.09^?	1.26 ± 0.11^?
antagomiR-203a-3p组	0.24 ± 0.10^{? # &}	2.15 ± 0.43^{? # &}	3.68 ± 0.38^{? # &}	5.12 ± 0.44^{? # &}	3.27 ± 0.41^{? # &}

组别	PIK3CA	p-PI3K/PI3K	p-AKT/AKT	Survivin
假手术组	0.50 ± 0.05	0.33 ± 0.05	0.41 ± 0.08	0.32 ± 0.04
模型组	1.00 ± 0.14^?	0.74 ± 0.10^?	0.89 ± 0.10^?	0.67 ± 0.13^?
antagomiR-NC组	1.04 ± 0.09^?	0.74 ± 0.11^?	0.92 ± 0.13^?	0.68 ± 0.14^?
antagomiR-203a-3p组	1.80 ± 0.32^{? # &}	1.34 ± 0.07^{? # &}	1.69 ± 0.29^{? # &}	1.33 ± 0.12^{? # &}

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

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