UBL4A alleviates the progression of intracerebral hemorrhage by regulating oxidative stress and mitochondrial damage.

IF 2.2 4区 农林科学 Q1 VETERINARY SCIENCES Experimental Animals Pub Date : 2024-06-07 DOI:10.1538/expanim.24-0035
Dan Li, Le Wang, Shufeng Shi, Xiaofeng Deng, Xuehan Zeng, Yunong Li, Shulin Li, Peng Bai
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Abstract

Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin Like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced ROS level and increased MnSOD activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.

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UBL4A通过调节氧化应激和线粒体损伤缓解脑出血的进展。
针灸对脑内出血(ICH)有明显的治疗作用,针灸调控的miR-34a-5p可减轻ICH患者的神经功能缺损。然而,其潜在机制尚不清楚。关于泛素样蛋白 4A(UBL4A)在 ICH 中的作用尚未进行研究。给 SD 大鼠注射自体血诱导 ICH,并用百会-穿刺-丘脑针刺治疗。针刺可提高 ICH 大鼠前肢放置试验得分,降低转角试验得分和脑含水量。组织病理学检查显示,针刺抑制了 ICH 引起的炎症,减少了受损神经元,增加了 UBL4A 的表达。在大鼠胚胎原代皮质神经元中,UBL4A 的过表达提高了细胞活力,抑制了细胞凋亡,降低了 ROS 水平,提高了 MnSOD 活性、线粒体膜电位和 mtDNA 水平。双荧光素酶测定显示,miR-34a-5p 与 UBL4A 结合。敲除 UBL4A 和 miR-34a-5p 的海明处理神经元的凋亡细胞和 ROS 水平都有所增加。我们首次证明了UBL4A对神经元凋亡的抑制作用,以及UBL4A和miR-34a-5p之间的调控关系。这项研究为治疗 ICH 提供了一个新的候选靶点,也为阐明针灸的分子机制提供了更多依据。今后,我们将对UBL4A对ICH的影响进行更深入的探讨。
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来源期刊
Experimental Animals
Experimental Animals 生物-动物学
CiteScore
2.80
自引率
4.20%
发文量
2
审稿时长
3 months
期刊介绍: The aim of this international journal is to accelerate progress in laboratory animal experimentation and disseminate relevant information in related areas through publication of peer reviewed Original papers and Review articles. The journal covers basic to applied biomedical research centering around use of experimental animals and also covers topics related to experimental animals such as technology, management, and animal welfare.
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