Zhou Na, Che Siyi, Liu Jiao, Jiang Zhenghong, Ren Luo, Liu Yin, Liu Enmei, Xie Jun
Department of Pediatrics, Bishan Hospital of Chongqing Medical University, Bishan County, Chongqing, China.
Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
J Thorac Dis. 2024 Jul 30;16(7):4607-4618. doi: 10.21037/jtd-24-752. Epub 2024 Jul 9.
Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation.
Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors () 1-9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-β (TRIF) were detected via Western blot analysis.
RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection.
Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.
穿心莲内酯磺化物（Andro-S）是一种传统中药，在中国常用于治疗小儿呼吸道感染。然而，其对呼吸道合胞病毒（RSV）感染的治疗效果尚未见报道。因此，我们旨在利用RSV感染诱导气道炎症的小鼠模型研究Andro-S的治疗效果。
免疫受损（经环磷酰胺处理）的BALB/c小鼠经鼻感染RSV，并从感染当天开始连续5天每天经鼻或腹腔注射Andro-S一次。使用苏木精和伊红染色评估肺组织的组织病理学变化。显微镜下测定支气管肺泡灌洗液（BALF）中的总炎症细胞计数以及巨噬细胞、淋巴细胞、中性粒细胞和嗜酸性粒细胞计数。使用酶联免疫吸附测定（ELISA）检测BALF中的干扰素-γ（IFN-γ）水平。用定量实时聚合酶链反应（qRT-PCR）测定肺组织中RSV核蛋白（N）和Toll样受体（）1-9的信使RNA水平。通过蛋白质印迹分析检测RSV N、RSV融合蛋白（F）、TLR2、TLR3和含TIR结构域的衔接蛋白诱导干扰素-β（TRIF）的蛋白水平。
RSV感染导致肺部炎症，表现为细支气管炎、肺泡炎和血管周围炎症；增加了炎症细胞数量；并提高了BALF中的IFN-γ水平。感染小鼠的肺部炎症与肺部RSV N水平呈正相关。经鼻给予Andro-S可显著下调肺组织中RSV N、RSV F、TLR3和TRIF蛋白表达，并改善感染动物的肺部炎症。然而，腹腔注射Andro-S对RSV感染引起的肺部炎症没有影响。
经鼻给予Andro-S可通过下调TLR3和TRIF抑制RSV复制并改善RSV感染诱导的肺部炎症。因此，经鼻给药可能是治疗RSV感染的合适给药方式。
