红红草苷通过ERβ/ bnip3介导的线粒体自噬激活减轻大鼠模型脑缺血再灌注损伤

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xing Rong, Peipei Lu, Yu Li, Hongxiang Wang, Yuanjia Yue, Huimin Wang, Zhao Ji, Lin Jiang
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引用次数: 0

摘要

本研究旨在评估红红草苷(SAL)对大鼠脑缺血再灌注损伤(CIRI)的神经保护作用,并阐明其潜在机制,重点研究雌激素受体β (ERβ)和BCL2相互作用蛋白3 (BNIP3)介导的线粒体自噬作为缺血性卒中潜在治疗靶点的作用。选取雌性Sprague-Dawley大鼠165只,随机分为11组,每组15只。其中一组作为对照组。其余动物进行双侧卵巢切除术,随后被分配到以下组:卵巢切除术,大脑中动脉闭塞/再灌注(MCAO/R),雌二醇对照组,ERβ抑制剂,两个抑制剂组(仅抑制剂和抑制剂加SAL),三个SAL治疗组(低,中线粒体分裂,高剂量)和阳性对照(依曲拉酮)。除对照组和单纯卵巢切除组外,其余各组均给予MCAO 1 h,再灌注24 h。评估神经功能、脑梗死体积、血脑屏障(BBB)通透性和脑含水量。评估组织病理学改变,并采用透射电镜检测自噬体。Western blot检测ERβ、BNIP3、nip3样蛋白X和微管相关蛋白1a / 1b轻链3的表达水平。在MCAO/R模型中,SAL和依达拉奉可显著降低神经功能损害、梗死体积、血脑屏障破坏和脑水肿。SAL处理上调ERβ和BNIP3表达,增强线粒体自噬相关蛋白水平。这些作用通过使用ERβ和线粒体分裂抑制剂而减弱,这表明sal介导的神经保护与ERβ/BNIP3信号轴的激活之间存在机制联系。SAL对大鼠CIRI具有神经保护作用,主要通过激活ERβ和增强bnip3介导的线粒体自噬。这些发现表明,调节ERβ/BNIP3通路可能是缺血性卒中的一种有希望的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Salidroside Attenuates Cerebral Ischemia-Reperfusion Injury via ERβ/BNIP3-Mediated Mitochondrial Autophagy Activation in a Rat Model

Salidroside Attenuates Cerebral Ischemia-Reperfusion Injury via ERβ/BNIP3-Mediated Mitochondrial Autophagy Activation in a Rat Model

Salidroside Attenuates Cerebral Ischemia-Reperfusion Injury via ERβ/BNIP3-Mediated Mitochondrial Autophagy Activation in a Rat Model

This study aimed to assess the neuroprotective effects of salidroside (SAL) on cerebral ischemia-reperfusion injury (CIRI) in a rat model and to elucidate the underlying mechanisms, with a focus on the role of estrogen receptor beta (ERβ) and BCL2 interacting protein 3 (BNIP3)-mediated mitochondrial autophagy as potential therapeutic targets in ischemic stroke. A total of 165 female Sprague-Dawley rats were randomly assigned into 11 groups (n = 15 per group). One group served as the control. The remaining animals underwent bilateral ovariectomy and were subsequently allocated into the following groups: ovariectomy-only, middle cerebral artery occlusion/reperfusion (MCAO/R), estradiol control, ERβ inhibitor, two inhibitor arms (inhibitor-only and inhibitor-plus-SAL), three SAL treatment groups (low, mediummitochondrial division, high dose), and a positive control (edaravone). All groups, except the control and ovariectomy-only groups, were subjected to MCAO for one hour followed by 24 h of reperfusion. Neurological function, cerebral infarct volume, blood-brain barrier (BBB) permeability, and brain water content were evaluated. Histopathological alterations were assessed, and transmission electron microscopy was employed to detect autophagosomes. Western blot analysis was performed to quantify protein expression levels of ERβ, BNIP3, NIP3-like protein X, and microtubule-associated protein 1 A/1B-light chain 3. Administration of SAL and edaravone significantly reduced neurological impairment, infarct volume, BBB disruption, and cerebral edema in the MCAO/R model. SAL treatment upregulated ERβ and BNIP3 expression and enhanced mitochondrial autophagy-associated protein levels. These effects were attenuated by the use of ERβ and mitochondrial division inhibitors, indicating a mechanistic link between SAL-mediated neuroprotection and activation of the ERβ/BNIP3 signaling axis. SAL exerts a neuroprotective effect against CIRI in rats, primarily through activation of ERβ and enhancement of BNIP3-mediated mitochondrial autophagy. These findings suggest that modulation of the ERβ/BNIP3 pathway may represent a promising therapeutic approach for ischemic stroke.

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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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