Nimodipine ameliorates cognitive dysfunction and neurological injury after subarachnoid hemorrhage in rats by upregulating microRNA-31-5p targeting hypoxia-inducible factor 1 subunit alpha inhibitor.

IF 2 4区 医学 Q3 PHYSIOLOGY
Journal of Physiology and Pharmacology Pub Date : 2024-12-01 Epub Date: 2025-02-03 DOI:10.26402/jpp.2024.6.03
S Lu, T T Chen, J K Zhang
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引用次数: 0

Abstract

Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke with high short-term mortality that can lead to cognitive and neurological impairment. Accurate and appropriate treatment strategies are urgently needed. Nimodipine (NDP) can not only improve blood circulation in SAH patients but also repair ischemic neuronal damage. microRNAs (miRNAs) are abundantly expressed in the brain and are involved in brain injury. Therefore, this study investigated the possible regulatory mechanisms of nimodipine on miRNAs in the process of cognitive dysfunction and neurological injury after SAH. The SAH rat model was established, miR-31-5p and hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) expressions were detected 48 h after modeling, and neurobehavioral function, neuronal apoptosis, activation of microglia, and inflammation were evaluated. Finally, the targeting relationship between miR-31-5p and HIF1AN was verified. The study findings explained that NDP treatment could effectively improve cognitive dysfunction, brain injury, neuronal injury, and neuroinflammation in SAH rats. SAH rats expressed down-regulated miR-31-5p and up-regulated HIF1AN. Overexpressing miR-31-5p or knocking down HIF1AN ameliorated cognitive dysfunction and brain damage in SHA rats. Mechanistically, nimodipine can promote miR-31-5p expression, and HIF1AN took part in the development of SAH as a downstream target gene of miR-31-5p. In conclusion, NDP ameliorates cognitive dysfunction and neurological damage in SHA rats by miR-31-5p/HIF1AN axis.

尼莫地平通过上调靶向缺氧诱导因子1亚单位α抑制剂的microRNA-31-5p,改善大鼠蛛网膜下腔出血后的认知功能障碍和神经损伤。
蛛网膜下腔出血(SAH)是一种短期死亡率高的出血性中风,可导致认知和神经功能障碍。迫切需要准确和适当的治疗策略。尼莫地平(NDP)不仅能改善SAH患者的血液循环,还能修复缺血性神经元损伤。microRNAs (miRNAs)在大脑中大量表达,并参与脑损伤。因此,本研究探讨尼莫地平在SAH后认知功能障碍和神经损伤过程中对mirna的可能调控机制。建立SAH大鼠模型,造模48 h后检测miR-31-5p和缺氧诱导因子1亚单位α抑制剂(HIF1AN)的表达,并评估神经行为功能、神经元凋亡、小胶质细胞活化和炎症反应。最后验证miR-31-5p与HIF1AN的靶向关系。研究结果说明NDP治疗可有效改善SAH大鼠的认知功能障碍、脑损伤、神经元损伤和神经炎症。SAH大鼠miR-31-5p表达下调,HIF1AN表达上调。过表达miR-31-5p或敲低HIF1AN可改善SHA大鼠的认知功能障碍和脑损伤。在机制上,尼莫地平可以促进miR-31-5p的表达,HIF1AN作为miR-31-5p的下游靶基因参与了SAH的发展。综上所述,NDP通过miR-31-5p/HIF1AN轴改善SHA大鼠的认知功能障碍和神经损伤。
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来源期刊
CiteScore
4.00
自引率
22.70%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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