Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice
Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice
复制标题
大黄酸通过 NF-κB 通路抑制 NLRP3 炎症小体激活，从而抑制人呼吸道合胞病毒引起的肺部炎症损伤
DOI：
10.3389/fphar.2019.01600
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发表时间：
2020-01-28
影响因子：
5.6
通讯作者：
Zhao, Xia
中科院分区：
文献类型：
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作者：
Shen, Cunsi;Zhang, Zhengguang;Zhao, Xia
大黄酸是传统中草药掌叶大黄中的蒽醌类活性成分之一，具有抗炎、抗氧化、抗肿瘤、抗病毒和保肝活性。人类呼吸道合胞病毒（RSV）是一种常见病毒，能够导致肺炎和支气管炎，通常可以在婴儿中看到。然而，到目前为止，大黄酸对RSV诱导的肺炎的影响仍然未知。由于NLRP 3炎性体被过度激活，在呼吸道的大多数病毒感染过程（包括RSV感染）中，它能够导致炎症反应和组织损伤。因此，我们设计了实验来揭示大黄酸是否可以通过抑制NLRP 3炎性小体激活来治疗RSV诱导的肺炎。本研究建立了呼吸道合胞病毒（RSV）致BALB/C小鼠肺炎模型。首先对小鼠肺组织进行病理学评价，并计算相应的肺指数。采用酶联免疫吸附试验（ELISA）、实时荧光定量PCR（RT-PCR）、免疫组化（IHC）和Western blot检测血清和肺组织中促炎介质及NLRP 3炎性体和NF-κ B通路相关蛋白（NLRP 3、ASC和Caspase-1）的表达。肺指数测定和肺组织病理学评价表明，大黄酸能减轻RSV引起的肺部感染和损伤。ELISA结果显示大黄酸能够减少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IL-1 β、IL-6、TNF-α、IL-18和IL-33。此外，大黄酸对RSV感染小鼠的免疫炎症反应有抑制作用，其机制可能与抑制NF-kB途径介导的NLRP 3炎性小体活化有关。综上所述，我们的研究结果表明，大黄酸可以有效地抑制RSV诱导的肺部炎症反应，同时强调大黄酸治疗可能是一种有希望的治疗RSV感染的肺部炎症和避免肺组织损伤的方法。
Rhein is one of active anthraquinone components in traditional Chinese herbal medicine Rheum palmatum L., 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-kappa B 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-1 beta, IL-6, TNF-alpha, 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 via NF-kB 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.