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丹酚酸联合三七总皂苷对脑缺血/再灌注大鼠神经血管单元及营养偶联相关的神经保护作用。

Neuroprotective effects of salvianolic acids combined with Panax notoginseng saponins in cerebral ischemia/reperfusion rats concerning the neurovascular unit and trophic coupling.

机构信息

School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, P. R. China.

Department of Traditional Chinese Medicine, The Baotou Central Hospital, Baotou, P. R. China.

出版信息

Brain Behav. 2024 Sep;14(9):e70036. doi: 10.1002/brb3.70036.


DOI:10.1002/brb3.70036
PMID:39295106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11410882/
Abstract

BACKGROUND: The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. METHODS: Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). RESULTS: Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and junctional adhesion molecule-1 (JAM-1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRβ and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. CONCLUSIONS: SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately.

摘要

背景:神经血管单元(NVU)和神经血管营养偶联(NVTC)在缺血性中风引起的脑损伤中发挥关键调节作用。丹酚酸(SAL)和三七总皂苷(PNS)在中国广泛用于治疗缺血性中风。本研究检测了 SAL 和 PNS 单独或联合使用时的神经保护作用。

方法:Wistar 大鼠随机分为以下几组:假手术组(Sham)、脑缺血再灌注组(I/R)、SAL 治疗组(SAL)、PNS 治疗组(PNS)、SAL+PNS 联合治疗组(SAL+PNS)和依达拉奉治疗组(EDA)。MCAO/R 模型建立后,每天治疗一次,共治疗两天。

结果:与 I/R 组相比,SAL、PNS 或 SAL+PNS 治疗可减小梗死面积,改善神经功能缺损评分,减少 Evans 蓝渗出,增加 CD31 和紧密连接蛋白(TJs)的表达,包括闭合蛋白-1(ZO-1)、闭合蛋白-2(ZO-2)和连接黏附分子-1(JAM-1)。此外,SAL、PNS 或 SAL+PNS 抑制小胶质细胞和星形胶质细胞的激活,减轻神经元和周细胞损伤。治疗还抑制了 GFAP/PDGFRβ 和 Collagen IV/GFAP 的 NVU 解离,同时上调了 BDNF/TrkB 和 BDNF/NeuN 的表达水平。

结论:SAL 和 PNS 显著改善了 I/R 损伤中 NVU 和 NVTC 的结构和功能障碍。SAL 和 PNS 联合使用的效果比单独使用时更为显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/a962cc33592d/BRB3-14-e70036-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/1a563c36d794/BRB3-14-e70036-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/aaa987a670c9/BRB3-14-e70036-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/484f75a43969/BRB3-14-e70036-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/9be35658516f/BRB3-14-e70036-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/6c91473170cc/BRB3-14-e70036-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/eb9440265e6d/BRB3-14-e70036-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/68ba27c66301/BRB3-14-e70036-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/a962cc33592d/BRB3-14-e70036-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/1a563c36d794/BRB3-14-e70036-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/aaa987a670c9/BRB3-14-e70036-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/484f75a43969/BRB3-14-e70036-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/3e71aa474424/BRB3-14-e70036-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/9be35658516f/BRB3-14-e70036-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/c5838e62590f/BRB3-14-e70036-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/6c91473170cc/BRB3-14-e70036-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/eb9440265e6d/BRB3-14-e70036-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/68ba27c66301/BRB3-14-e70036-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/11410882/a962cc33592d/BRB3-14-e70036-g001.jpg

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[1]
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[2]
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JAMA. 2023-2-28

[3]
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Front Pharmacol. 2023-1-9

[4]
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[5]
Investigation into the potential mechanism and molecular targets of Fufang Xueshuantong capsule for the treatment of ischemic stroke based on network pharmacology and molecular docking.

Front Pharmacol. 2022-9-15

[6]
Challenges and strategies in progress of drug delivery system for traditional Chinese medicine et (Danshen).

Chin Herb Med. 2020-11-14

[7]
The neurovascular unit and systemic biology in stroke - implications for translation and treatment.

Nat Rev Neurol. 2022-10

[8]
Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway.

Phytother Res. 2022-10

[9]
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[10]
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