Tanshinone IIA Alleviates Early Brain Injury after Subarachnoid Hemorrhage in Rats by Inhibiting the Activation of NF-κB/NLRP3 Inflammasome.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Biological & pharmaceutical bulletin Pub Date : 2024-01-26 Epub Date: 2023-12-06 DOI:10.1248/bpb.b23-00519
Fanhui Yang, Ningshuai Ma, Suping Li, Fei Chen, Xiaohong Huang, Li Zhao, Lingzhi Cao
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引用次数: 0

Abstract

The abnormal activation of the nuclear factor-kappa B (NF-κB)/nod-like receptor family-pyrin domain-containing 3 (NLRP3) signaling pathway is closely related to early brain injury after subarachnoid hemorrhage (SAH). Targeting the NLRP3-inflammasome has been considered an efficient therapy for the local inflammatory response after SAH. Tanshinone IIA (Tan IIA), a major component extracted from Salvia miltiorrhiza, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the effect and mechanism of Tan IIA on early brain injury after SAH. In vivo SAH injury was established by endovascular perforation technique in Sprague-Dawley rats. Limb-placement test and corner turning test were used to measure the behavior. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, hematoxylin-eosin (H&E) staining, and immunofluorescence were used to evaluate the nerve damage. Real-time RT quantitative PCR (RT-qPCR) was used to quantify the levels of inflammatory factors. Western blot was performed for the activation of the NF-κB/NLRP3 pathway. An in vitro SAH model was used to validate the conclusion. We found that the neurobehavioral impairment and cerebral edema in SAH model rats given Tan IIA were alleviated. Further study demonstrated that Tan IIA could inhibit SAH-secondary neuronal apoptosis around hematoma and alleviate brain injury. Tan IIA down-regulated the expression of interleukin-6 (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α, and inhibited the activation of NF-κB. And the overexpression of pro-inflammatory factors NLRP3, IL-1β, and IL-18 induced after SAH was also reversed by Tan IIA. In conclusions, Tan IIA could inhibit the NF-κB/NLRP3 inflammasome activation to protect and ameliorate SAH-followed early brain injury, and may be a preventive and therapeutic strategy against SAH.

丹参酮IIA通过抑制NF-κB/NLRP3炎性体的激活,减轻大鼠蛛网膜下腔出血后早期脑损伤。
NF-κB/NLRP3信号通路异常激活与蛛网膜下腔出血(SAH)后早期脑损伤密切相关。靶向nlrp3炎性小体被认为是治疗SAH后局部炎症反应的有效方法。丹参酮ⅡA (TanⅡA)是从丹参中提取的一种主要成分,据报道具有抗炎作用。本研究旨在探讨TanⅡA对SAH后早期脑损伤的影响及其机制。采用血管内穿孔技术在Sprague-Dawley大鼠体内建立SAH损伤。采用肢体放置试验和转角试验对其行为进行测量。采用TUNEL染色、HE染色、免疫荧光法评价神经损伤程度。采用RT-qPCR定量检测炎症因子水平。Western blot检测NF-κB/ nod样受体家族pyrin domain-containing 3 (NLRP3)通路的激活情况。采用体外SAH模型对结论进行验证。我们发现坦ⅡA能减轻SAH模型大鼠的神经行为障碍和脑水肿。进一步研究表明,TanⅡA可抑制sah -继发性血肿周围神经元凋亡,减轻脑损伤。TanⅡA下调IL-6、单核细胞趋化蛋白-1 (MCP-1)、TNF-α的表达,抑制NF-κB的活化。TanⅡA也能逆转SAH后促炎因子NLRP3、IL-1β和IL-18的过表达。综上所述,TanⅡA可以抑制NF-κB/NLRP3炎性小体的激活,保护和改善SAH后的早期脑损伤,可能是一种预防和治疗SAH的策略。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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