安宫牛黄丸预处理通过SIRT1-H4K16ac轴抑制过度自噬，减轻脑缺血再灌注损伤。

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-01-31 DOI:10.1016/j.jep.2024.119214

Lihan Wang , Jingyi Hou , He Xu , Qingqing Cai , Liangliang Tian , Xueli Li , Jingjing Zhang , Hongjun Yang

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引用次数: 0

摘要

民族药理学相关性：脑缺血再灌注损伤（CIRI）是脑卒中治疗的重要病理过程。安宫牛黄丸（ANP）源于温冰条，具有神经保护作用，但其缓解CIRI的机制尚不清楚。研究目的：本研究旨在通过乙酰组学和蛋白质组学研究ANP减轻CIRI的机制。材料和方法：采用大脑中动脉闭塞法（MCAO）建立CIRI模型。采用神经功能缺损评分、TTC染色、区域脑血流量（rCBF）测定和TUNEL染色评估ANP预处理对CIRI的神经保护作用。进行了乙酰组学和蛋白质组学分析，以确定ANP降低CIRI的潜在机制。最后，使用SIRT1抑制剂EX527验证了SIRT1- h4k16ac介导的自噬在ANP神经保护作用中的作用。结果：ANP预处理显著降低神经功能缺损评分和脑梗死体积，增加rCBF，减少细胞凋亡。乙酰组学和蛋白质组学结果表明，ANP通过调控H4K16ac在转录水平上调控自噬。免疫荧光和western blot分析证实ANP促进sirtuin 1 （SIRT1）的积累。ANP预处理降低H4K16ac水平，降低LC3B-II/I比值，上调SQSTM1/p62，抑制ATG5和ATG7的表达。EX527抵消这些影响的能力强调了SIRT1-H4K16ac通路在介导ANP对CIRI的保护作用中的重要性。结论：ANP通过调节SIRT1-H4K16ac通路发挥神经保护作用，从而阻止CIRI引发的过度自噬。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Angong Niuhuang Pill pretreatment alleviates cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through the SIRT1-H4K16ac axis

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Angong Niuhuang Pill pretreatment alleviates cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through the SIRT1-H4K16ac axis

Ethnopharmacological relevance

Cerebral ischemia-reperfusion injury (CIRI) is an important pathological process in stroke treatment. Angong Niuhuang Pill (ANP), originating from Wenbing Tiaobian, has been shown to have neuroprotective effects, but its mechanism in alleviating CIRI remains unclear.

Aim of the study

This study aimed to elucidate the mechanism by which ANP alleviates CIRI using acetylomics and proteomics.

Materials and methods

The CIRI model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scoring, TTC staining, regional cerebral blood flow (rCBF) measurement, and TUNEL staining were used to assess the neuroprotective effects of ANP pretreatment on CIRI. Acetylomics and proteomics analyses were performed to identify the potential mechanisms by which ANP reduces CIRI. Finally, the role of SIRT1-H4K16ac-mediated autophagy in the neuroprotective effects of ANP was validated by using a SIRT1 inhibitor, EX527.

Results

ANP pretreatment markedly lowered neurological deficit scores and cerebral infarct volumes, increased rCBF, and reduced apoptosis. Acetylomics and proteomics results suggested that ANP regulated autophagy at the transcriptional level by modulating H4K16ac. Immunofluorescence and Western blot analyses confirmed that ANP promoted the accumulation of sirtuin 1 (SIRT1). Specifically, ANP pretreatment reduced H4K16ac levels, decreased LC3B-II/I ratios, upregulated SQSTM1/p62, and suppressed the expression of ATG5 and ATG7. The ability of EX527 to counteract these effects underscored the importance of the SIRT1-H4K16ac pathway in mediating the protective action of ANP against CIRI.

Conclusions

ANP provides neuroprotection by modulating the SIRT1-H4K16ac pathway, thereby preventing the excessive autophagy triggered by CIRI.

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.