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低分子量肝素通过抑制TLR4-MyD88-NF-κB信号通路改善急性鼻窦炎大鼠的炎症状态。

Low Molecular Weight Heparin Improves the Inflammatory State of Acute Sinusitis Rats Through Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

作者信息

Wu Tong, He Sihan, Jiao Zan, Liang Xiang, Chen Yu, Liu Huow, Zhang Yongq, He GuangX

机构信息

Department of Otolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China.

Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Front Pharmacol. 2021 Nov 17;12:726630. doi: 10.3389/fphar.2021.726630. eCollection 2021.

Abstract

Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied. SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with . Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status. Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression. This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

摘要

低分子量肝素(LMWH)是一种对促血管生成因子具有亲和力的天然硫酸化糖胺聚糖,通过对普通肝素(UFH)进行化学或酶解聚而产生。LMWH以其抗凝作用而闻名,最近有报道称它对结肠炎、心肌炎和气道炎症具有强大的抗炎作用。然而,作为一种新开发的药物,其在上呼吸道炎症中的抗炎机制尚未得到充分研究。将SD大鼠随机分为对照组和实验组。通过用混合有……的膨胀海绵建立急性鼻窦炎模型来构建实验组。然后给实验组大鼠皮下注射不同浓度的LMWH。连续注射七天后,处死部分大鼠,采集血液和鼻黏膜样本以确定其炎症状态。其余的急性鼻窦炎大鼠被随机选择用生理盐水或与不同浓度LMWH混合的生理盐水进行一周的鼻腔冲洗。一周后,处死大鼠,采集血液和鼻黏膜样本以确定炎症状态。模型组大鼠鼻黏膜有明显炎症。实验组鼻黏膜炎症损伤程度低于实验对照组,证明LMWH对鼻黏膜有保护作用,且该作用与剂量相关。用与LMWH混合的生理盐水冲洗鼻腔可提高抗炎效果。急性鼻窦炎大鼠模型中与TLR4-MyD88-NF-κB信号通路相关的蛋白被激活,而LMWH可显著抑制其表达。这是关于LMWH在急性上呼吸道炎症中抗炎作用的首次报道,并对其抗炎机制进行了解释。这些发现为其潜在的抗肿瘤作用提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/139e/8635784/2302ef45b6d3/fphar-12-726630-g001.jpg

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