Luo Shanjun, Gan Lianfang, Liu Shengxing, Zhong Lifan, Chen Meiling, Zhang Hong, Li Jiankang, Huang Ling, Lv Chuanzhu
Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, China.
Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences, Hainan Medical University, Haikou, China.
J Thorac Dis. 2022 Feb;14(2):474-493. doi: 10.21037/jtd-22-126.
Reduning (RDN) is a common Chinese medicine preparation with antibacterial, anti-inflammatory, antiviral and immunomodulatory effects in respiratory infectious diseases. Clinically, it is used in combination with antibiotics, but its synergistic effect and mechanism in treating severe pneumonia remain unclear.
A rat model of severe pneumonia and an coculture model consisting of A549 and THP-1 cells were used to observe the synergistic effect of RDN on severe pneumonia. The inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA). The localization of Aryl hydrocarbon receptor (AhR) in A549 cells was observed by immunofluorescence, and the interaction of AhR and signal transducer and activator of transcription 3 (STAT3) proteins was observed by co-immunoprecipitation. AhR-Src tyrosine kinase (Src)-STAT3 pathway in rats and A549 cells were examined by Western Blot. Histopathological changes were observed by Hematoxylin-eosin (HE) staining, X-ray and survival rates were used to evaluate the effects of paclitaxel on severe pneumonia rats.
RDN regulation of Src-STAT3-interleukin 10 (IL-10) signaling pathway activation and macrophage polarization were mediated through the nuclear receptor AhR. The expression of AhR was significantly increased after RDN treatment, and this effect was accompanied by STAT3 expression increasing. Coimmunoprecipitation confirmed an interaction between AhR and STAT3 and upregulated IL-10 expression. Silencing AhR decreased Src, STAT3, and IL-10 expression. RDN activated AhR and increased Src, STAT3, and IL-10 expression. In addition, RDN regulated the polarization of macrophages RDN combined with cefmetazole sodium significantly reduced the pulmonary bacterial load, alleviated lung injury, and reduced o inflammatory factors expression, improving their survival.
RDN can synergistically enhance the effect of cefmetazole sodium treatment in severe pneumonia, and the mechanism may involve increasing the expression level of IL-10 mediated through the AhR-Src-STAT3 pathway, driving the polarization of macrophages, and attenuating the cytokine storm to control inflammation in severe pneumonia.
热毒宁（RDN）是一种常见的中药制剂，对呼吸道传染病具有抗菌、抗炎、抗病毒和免疫调节作用。临床上，它与抗生素联合使用，但其在治疗重症肺炎中的协同作用及机制尚不清楚。
采用重症肺炎大鼠模型以及由A549和THP-1细胞组成的共培养模型，观察热毒宁对重症肺炎的协同作用。通过酶联免疫吸附测定（ELISA）检测炎性细胞因子。采用免疫荧光法观察芳烃受体（AhR）在A549细胞中的定位，通过免疫共沉淀观察AhR与信号转导子和转录激活子3（STAT3）蛋白的相互作用。采用蛋白质免疫印迹法检测大鼠和A549细胞中的AhR-Src酪氨酸激酶（Src）-STAT3通路。通过苏木精-伊红（HE）染色观察组织病理学变化，利用X射线和生存率评估紫杉醇对重症肺炎大鼠的影响。
热毒宁对Src-STAT3-白细胞介素10（IL-10）信号通路激活和巨噬细胞极化的调节是通过核受体AhR介导的。热毒宁治疗后AhR的表达显著增加，且这种作用伴随着STAT3表达的增加。免疫共沉淀证实AhR与STAT3之间存在相互作用，并上调了IL-10的表达。沉默AhR可降低Src、STAT3和IL-10的表达。热毒宁激活AhR并增加Src、STAT3和IL-10的表达。此外，热毒宁调节巨噬细胞的极化。热毒宁与头孢美唑钠联合使用可显著降低肺部细菌载量，减轻肺损伤，降低炎性因子表达，提高其生存率。
热毒宁可协同增强头孢美唑钠治疗重症肺炎 的效果，其机制可能涉及通过AhR-Src-STAT3通路增加IL-10的表达水平，驱动巨噬细胞极化，减轻细胞因子风暴以控制重症肺炎中的炎症。
