Protective effects of Zishen Huoxue recipe against neuronal injury in the neurovascular unit of rats with vascular dementia by interfering with inflammatory cascade-induced pyroptosis

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2023-06-26 DOI:10.1016/j.npep.2023.102358

Ting Yao , Le Xie , Yao Xie , Jinlin Jiang , Qian Deng , Jie Wang , Lu Liu , Dahua Wu

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引用次数: 1

Abstract

Objective

Chinese herbal formulas show considerable therapeutic benefits in dementia. This study specifically explored the protective action of Zishen Huoxue recipe on the neurovascular unit (NVU) of rats with vascular dementia (VD).

Methods

VD rat models were established by permanent bilateral common carotid artery occlusion and treated with Zishen Huoxue recipe. In vitro glucose‑oxygen deprivation (OGD)-injured NVU models were established and treated with miR-124-3p agomir or rat medicated serum. The neurological damage, histopathological changes, and neuronal injury in the rat hippocampus were assessed using Morris water maze test and histological stainings. Expression of miR-124-3p was determined using RT-qPCR. The blood-brain barrier/NVU injury, cell pyroptosis, NLRP3 inflammasome activation, and release of inflammatory factors were analyzed mainly by immunofluorescence analysis, TUNEL staining, Western blot, and ELISA. QS-21 (an NLRP3 activator) was used to verify the role of miR-124-3p/NLRP3.

Results

Zishen Huoxue recipe ameliorated the learning/memory deficits, neuronal injury, NVU insults, cell pyroptosis, activation of NLRP3 inflammasome, and extensive secretion of lactate dehydrogenase/IL-1β/IL-18 in VD rats. miR-124-3p was downregulated in VD rats but upregulated after treatment of this recipe. miR-124-3p overexpression ameliorated NVU insults, reduced cell pyroptosis, lowered NLRP3 inflammasome activation, and suppressed inflammatory responses in OGD-injured NVU models. NLRP3 inflammasome activation partly counteracted the amelioration effect of miR-124-3p on pyroptosis. Zishen Huoxue recipe could upregulate miR-124-3p to suppress pyroptosis and protect NVU function.

Conclusion

Zishen Huoxue recipe can upregulate miR-124-3p expression to repress the inflammatory cascade-evoked pyroptosis, thereby protecting against neuronal injury in the NVU of VD rats.

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滋肾活血方通过干预炎症级联性焦亡对血管性痴呆大鼠神经血管单元损伤的保护作用

目的中草药配方对痴呆症具有显著的治疗作用。本研究旨在探讨滋肾活血方对血管性痴呆（VD）大鼠神经血管单位（NVU）的保护作用。建立了体外糖氧剥夺（OGD）损伤的NVU模型，并用miR-124-3p阿戈米或大鼠药物血清治疗。使用Morris水迷宫试验和组织学染色评估大鼠海马的神经损伤、组织病理学变化和神经元损伤。使用RT-qPCR测定miR-124-3p的表达。主要通过免疫荧光分析、TUNEL染色、Western印迹和ELISA分析血脑屏障/NVU损伤、细胞焦下垂、NLRP3炎症小体激活和炎症因子释放。结果滋肾活血方可改善VD大鼠学习记忆障碍、神经元损伤、NVU损伤、细胞焦下垂、NLRP3炎症小体激活以及乳酸脱氢酶/IL-1β/IL-18的大量分泌。miR-124-3p在VD大鼠中下调，但在该配方治疗后上调。miR-124-3p过表达改善了OGD损伤的NVU模型中的NVU损伤，减少了细胞焦下垂，降低了NLRP3炎症小体的激活，并抑制了炎症反应。NLRP3炎症小体的激活部分抵消了miR-124-3p对pyroptosis的改善作用。滋肾活血方可上调miR-124-3p抑制pyroptosis，保护NVU功能。结论滋肾活血方可上调miR-124-3p的表达，抑制炎症级联反应诱发的pyroptosis，从而保护VD大鼠NVU免受神经元损伤。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.