The synergistic Reduning and cefmetazole sodium treatment of severe pneumonia is mediated by the AhR-Src-STAT3 pathway.
The synergistic Reduning and cefmetazole sodium treatment of severe pneumonia is mediated by the AhR-Src-STAT3 pathway.
复制标题
热舒宁和头孢美唑钠协同治疗重症肺炎是由AhR-Src-STAT3通路介导的。
DOI：
10.21037/jtd-22-126
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发表时间：
2022-03
影响因子：
2.5
通讯作者：
Lv C
中科院分区：
文献类型：
--
作者：
Luo S;Gan L;Liu S;Zhong L;Chen M;Zhang H;Li J;Huang L;Lv C
热毒宁是呼吸道感染性疾病中常用的中药制剂，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，但其治疗重症肺炎的协同作用和机制尚不清楚。采用大鼠重症肺炎模型和体外A549与THP-1细胞共培养模型，观察RDN对重症肺炎的协同作用。采用酶联免疫吸附试验（ELISA）检测炎性细胞因子。免疫荧光法观察芳烃受体（AhR）在A549细胞中的定位，免疫共沉淀法观察AhR与信号转导子和转录激活子3（STAT 3）蛋白的相互作用。Western Blot检测大鼠及A549细胞中AhR-Src酪氨酸激酶（Src）-STAT 3通路的变化。HE染色观察组织学改变，X线片观察紫杉醇对重症肺炎大鼠的治疗作用，并观察存活率。RDN通过核受体AhR介导Src-STAT 3-IL-10信号通路激活和巨噬细胞极化。RDN处理后，AhR表达明显增加，同时伴有STAT 3表达的增加。免疫共沉淀证实了AhR和STAT 3之间的相互作用，并上调IL-10的表达。沉默AhR降低Src、STAT 3和IL-10表达。RDN激活AhR并增加Src、STAT 3和IL-10的表达。此外，RDN可调节巨噬细胞的极化，与头孢美唑钠联合应用可显著降低肺内细菌负荷，减轻肺损伤，降低炎症因子表达，提高其生存率。RDN可协同增强头孢美唑钠治疗重症肺炎的疗效，其机制可能涉及通过AhR-Src-STAT 3通路提高IL-10的表达水平，驱动巨噬细胞极化，减弱细胞因子风暴，从而控制重症肺炎的炎症反应。
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 in vitro 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.
热毒宁注射液作为中药药理靶点的通路研究
影响因子：
3.7
作者：
Liu J;Sun K;Zheng C;Chen X;Zhang W;Wang Z;Shar PA;Xiao W;Wang Y
通讯作者：
Wang Y