泛素样蛋白 4A 通过调节氧化应激和线粒体损伤缓解脑出血的进展。
Ubiquitin-like 4A alleviates the progression of intracerebral hemorrhage by regulating oxidative stress and mitochondrial damage.
机构信息
Department of Acupuncture, Beijing University of Chinese Medicine Third Affiliated Hospital, No. 51, Xiaoguan Street, Anwai, Chaoyang District, Beijing 100029, P.R. China.
First Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6, Zone 1, Fangxingyuan, Fengtai District, Beijing, P.R. China.
出版信息
Exp Anim. 2024 Oct 23;73(4):421-432. doi: 10.1538/expanim.24-0035. Epub 2024 Jun 7.
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 reactive oxygen species (ROS) level and increased manganese superoxide dismutase (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.
针刺对脑出血(ICH)有明显的治疗作用。研究发现,针刺调节的 miR-34a-5p 可减轻 ICH 引起的神经功能缺损。然而,其潜在机制尚不清楚。泛素样 4A(UBL4A)在 ICH 中尚未被研究过。SD 大鼠被注入自体血以诱导 ICH,并接受百会透曲池针刺治疗。针刺可提高 ICH 大鼠的前肢放置试验评分,降低转角试验评分和脑含水量。组织病理学检查显示,针刺抑制了 ICH 诱导的炎症,减少了受损神经元的数量,并增加了 UBL4A 的表达。UBL4A 的过表达增加了细胞活力,抑制了细胞凋亡,降低了活性氧(ROS)水平,并提高了大鼠胚胎原代皮质神经元的锰超氧化物歧化酶(MnSOD)活性、线粒体膜电位和 mtDNA 水平。miR-34a-5p 敲低增加了血红素处理神经元中的 UBL4A 表达、细胞凋亡率和 ROS 水平。双荧光素酶报告基因实验显示 miR-34a-5p 与 UBL4A 结合。血红素处理神经元中 UBL4A 和 miR-34a-5p 敲低增加了凋亡细胞和 ROS 水平。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。本研究为 ICH 的治疗提供了新的候选靶点,并为阐明针刺的分子机制提供了更多依据。在未来,我们将对 UBL4A 对 ICH 的影响进行更深入的探索。