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大黄酸通过抑制小鼠NLRP3炎性小体激活的NF-κB途径抑制人呼吸道合胞病毒诱导的肺部炎性损伤

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation NF-κB Pathway in Mice.

作者信息

Shen Cunsi, Zhang Zhengguang, Xie Tong, Ji Jianjian, Xu Jianya, Lin Lili, Yan Jing, Kang An, Dai Qigang, Dong Yingmei, Shan Jinjun, Wang Shouchuan, Zhao Xia

机构信息

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Front Pharmacol. 2020 Jan 28;10:1600. doi: 10.3389/fphar.2019.01600. eCollection 2019.

DOI:10.3389/fphar.2019.01600
PMID:32047436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6997271/
Abstract

Rhein is one of active anthraquinone components in traditional Chinese herbal medicine , possessing anti-inflammatory, antioxidant, antitumor, antiviral, and hepatoprotective activities. Human respiratory syncytial virus (RSV), a common virus, is able to result in pneumonia and bronchitis, which usually can be seen in infants. However, so far the effects of Rhein on RSV-induced pneumonia are still unknown. As the NLRP3 inflammasome is activated excessively, it is able to lead to inflammatory response and tissue injury in most viral infection process (including RSV infection) of respiratory tract. Therefore, we designed experiments to reveal whether Rhein can treat RSV-induced pneumonia by inhibiting NLRP3 inflammasome activation. In present research, we established the pneumonia model of BALB/C mice caused by RSV. First of all, the pathology of lung tissue and the weight of mice were evaluated, and the corresponding lung index was calculated. Additionally, the expression of pro-inflammatory mediators in serum and lung tissues, and related proteins (NLRP3, ASC and Caspase-1) of NLRP3 inflammasome and NF-κB pathway were detected by Enzyme-linked immunosorbent assay (ELISA), Real-time PCR (RT-PCR), Immunohistochemistry (IHC), and Western blot (WB), respectively. The determination of lung index and lung tissue pathological evaluation revealed that Rhein was able to alleviate lung infection and injury caused by RSV. The results of ELISA showed that Rhein was able to reduce the release of pro-inflammatory cytokines in the serum and lung tissues of RSV-induced BALB/c mice, including IL-1β, IL-6, TNF-α, IL-18, and IL-33. Additionally, it was revealed that Rhein inhibited the immune inflammatory response of RSV-infected mice, which was likely to be associated with the inhibition the NLRP3 inflammasome activation NF-κB pathway. To sum up, our results indicated that Rhein may inhibit RSV-induced pulmonary inflammatory response effectively; meanwhile, it is emphasized that Rhein therapy is likely to be a promising treatment on the RSV-infected lung inflammation and avoidance of lung tissue damage.

摘要

大黄酸是传统中草药中活性蒽醌成分之一,具有抗炎、抗氧化、抗肿瘤、抗病毒和保肝活性。人呼吸道合胞病毒(RSV)是一种常见病毒,可导致肺炎和支气管炎,常见于婴儿。然而,迄今为止,大黄酸对RSV诱导的肺炎的影响仍不清楚。由于NLRP3炎性小体过度激活,在大多数呼吸道病毒感染过程(包括RSV感染)中会导致炎症反应和组织损伤。因此,我们设计实验以揭示大黄酸是否能通过抑制NLRP3炎性小体激活来治疗RSV诱导的肺炎。在本研究中,我们建立了由RSV引起的BALB/C小鼠肺炎模型。首先,评估肺组织病理学和小鼠体重,并计算相应的肺指数。此外,分别通过酶联免疫吸附测定(ELISA)、实时荧光定量聚合酶链反应(RT-PCR)、免疫组织化学(IHC)和蛋白质免疫印迹法(WB)检测血清和肺组织中促炎介质的表达以及NLRP3炎性小体和NF-κB通路的相关蛋白(NLRP3、ASC和半胱天冬酶-1)。肺指数测定和肺组织病理学评估表明,大黄酸能够减轻RSV引起的肺部感染和损伤。ELISA结果显示,大黄酸能够降低RSV诱导的BALB/c小鼠血清和肺组织中促炎细胞因子的释放,包括白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、白细胞介素-18和白细胞介素-33。此外,结果表明大黄酸抑制RSV感染小鼠的免疫炎症反应,这可能与抑制NLRP3炎性小体激活的NF-κB通路有关。综上所述,我们的结果表明大黄酸可能有效抑制RSV诱导的肺部炎症反应;同时,强调大黄酸治疗可能是治疗RSV感染引起的肺部炎症和避免肺组织损伤的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7780/6997271/d2d77e9b9cc0/fphar-10-01600-g007.jpg
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