miRNA-105 Attenuates Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Apoptosis and Necroptosis

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Junyan Liu, Hui Li, Yi Qu, Shiping Li, Fengyan Zhao
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Abstract

Apoptosis and necroptosis contribute significantly to cell death in hypoxic-ischemic encephalopathy (HIE). While microRNA-105 (miR-105) is known to suppress both apoptosis and necroptosis in cardiac ischemia, its role in HIE remains unclear. This study investigated the effects of miR-105 on apoptosis and necroptosis in a neonatal rat model of HIE. MiR-105 agomir was administered intracerebroventricularly 6 h post-hypoxic-ischemia (HI). The characteristic apoptosis-related proteins (BNIP3, cleaved caspase 3), necroptosis mediators (RIP3, p-RIP3, p-RIP1, p-MLKL), cerebral infarction, and neurological deficits were analyzed. Results showed miR-105 was significantly downregulated in cerebral cortex from 6 to 48 h post-HI, concurrent with increased BNIP3 and RIP3 expression, and elevated apoptosis and necroptosis, at both 24 and 48 h. MiR-105 agomir treatment suppressed BNIP3 and RIP3 expression, reduced apoptosis and necroptosis, attenuated infarct volume, lowered neurological severity score, and improved spatial learning and memory abilities. In conclusion, miR-105 alleviates HI brain injury in neonatal rats by simultaneously inhibiting apoptosis and necroptosis, highlighting its potential as therapeutic agent for HIE.

Abstract Image

miRNA-105通过抑制凋亡和坏死下垂减轻新生大鼠缺氧缺血性脑损伤。
缺氧缺血性脑病(HIE)中细胞凋亡和坏死下垂是导致细胞死亡的重要因素。虽然已知microRNA-105 (miR-105)在心脏缺血中抑制细胞凋亡和坏死下垂,但其在HIE中的作用尚不清楚。本研究探讨了miR-105对新生儿大鼠HIE模型中细胞凋亡和坏死下垂的影响。在缺氧缺血(HI)后6小时脑室内给予MiR-105 agomir。分析特征性凋亡相关蛋白(BNIP3、cleaved caspase 3)、坏死坏死介质(RIP3、p-RIP3、p-RIP1、p-MLKL)、脑梗死和神经功能缺损。结果显示,在hi后6 - 48 h, miR-105在大脑皮层中显著下调,同时在24和48 h, BNIP3和RIP3表达增加,凋亡和坏死升高。miR-105 agomir治疗抑制BNIP3和RIP3表达,减少凋亡和坏死,减轻梗死体积,降低神经系统严重程度评分,改善空间学习和记忆能力。综上所述,miR-105通过同时抑制细胞凋亡和坏死下垂减轻新生大鼠HI脑损伤,突出了其作为HIE治疗剂的潜力。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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