State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, PR China; Department of Intensive Care Unit, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, PR China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, PR China.
J Ethnopharmacol. 2021 Nov 15;280:114128. doi: 10.1016/j.jep.2021.114128. Epub 2021 Apr 16.
Influenza virus infection is widely believed to cause mild symptoms, but can lead to high mortality and severe disease complicated by secondary bacterial pneumonia. Traditional Chinese medicine (TCM) has been proposed as a promising agent to treat respiratory viral infections. A herbal formula Lianhuaqingwen capsule (LHQW) comprising two prescriptions: Maxing Shigan decoction and Yinqiao San, has been used clinically to treat respiratory infection with immune regulatory effects. However, little is known about the capacity of LHQW against influenza-induced secondary bacterial pneumonia.
This study aimed to evaluate the efficacy and underlying mechanism of LHQW on influenza A virus A/PR/8/34 (PR8) secondary methicillin-resistant Staphy-lococcus aureus (MRSA) infection.
The anti-adhesion activity of LHQW against PR8-induced MRSA infection was assessed in human lung epithelial (A549) cells and the effect of LHQW on the expression of intracellular adhesion molecule 1 (ICAM-1) was detected. Also, the mRNA expression levels of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation in PR8-infected A549 cells were determined. The body weight change, survivals, viral titers, colonies and the pathological parameters after LHQW treatment in severe pneumonia model have all been systematically determined.
LHQW significantly reduced the adhesion of MRSA to PR8-infected A549 cells in a dose-dependent manner by suppressing the up-regulation of bacterial receptors. LHQW also markedly declined the overexpression of IL-6, IL-8, and TNF-α induced by LPS stimulated-A549 cells following influenza virus infection. Furthermore, the abnormal changes of lung index in dual-infection mice were relieved after administered with LHQW in preventive and therapeutic mode, but with no significantly difference (P > 0.05). LHQW could not effectively improve survival rate or prolong the survival time of mice (P > 0.05). LHQW (1000 mg/kg/d) administered prophylactically significantly decreased the lung viral titers (P < 0.05), slightly downregulated IL-6 but TNF-α, IL-1β levels and improved lung pathological inflammation including neutrophil infiltration, necrosis, which is consistent with the expression of inflammatory factors.
LHQW inhibited influenza-induced bacterial adhesion by down-regulating the adhesion molecules with the improvement trend on severe pneumonia, indicating that it can be used as an adjuvant medication in severe viral-bacterial pneumonia therapy rather than as a single medication.
人们普遍认为流感病毒感染只会引起轻微症状，但它也可能导致高死亡率和严重疾病，并且可能伴有继发性细菌性肺炎。传统中药（TCM）已被提出作为一种有前途的治疗呼吸道病毒感染的药物。一种由两个方剂组成的草药配方连花清瘟胶囊（LHQW），包括麻杏石甘汤和银翘散，已在临床上用于治疗呼吸道感染，并具有免疫调节作用。然而，目前对于 LHQW 对抗流感病毒引起的继发性耐甲氧西林金黄色葡萄球菌（MRSA）感染的能力知之甚少。
本研究旨在评估 LHQW 对甲型流感病毒 A/PR/8/34（PR8）继发耐甲氧西林金黄色葡萄球菌（MRSA）感染的疗效和作用机制。
在人肺上皮（A549）细胞中评估 LHQW 对 PR8 诱导的 MRSA 感染的抗黏附活性，并检测 LHQW 对细胞间黏附分子 1（ICAM-1）表达的影响。此外，还测定了 PR8 感染的 A549 细胞在脂多糖（LPS）刺激下炎症细胞因子的 mRNA 表达水平。系统测定 LHQW 治疗严重肺炎模型后体重变化、存活率、病毒滴度、菌落和病理参数。
LHQW 以剂量依赖性方式显著降低了 MRSA 与 PR8 感染的 A549 细胞的黏附，抑制了细菌受体的上调。LHQW 还显著下调了流感病毒感染后 LPS 刺激的 A549 细胞中过度表达的 IL-6、IL-8 和 TNF-α。此外，在预防性和治疗性给药模式下，LHQW 可减轻双重感染小鼠肺部指数的异常变化，但差异无统计学意义（P>0.05）。LHQW 不能有效提高小鼠的存活率或延长其存活时间（P>0.05）。预防性给予 LHQW（1000mg/kg/d）可显著降低肺病毒滴度（P<0.05），轻度下调 IL-6，但 TNF-α、IL-1β 水平，并改善肺部病理炎症，包括中性粒细胞浸润、坏死，这与炎症因子的表达一致。
LHQW 通过下调黏附分子抑制流感诱导的细菌黏附，对严重肺炎有改善趋势，表明它可作为严重病毒性-细菌性肺炎治疗的辅助药物，而不是单一药物。
