Mechanism of Mahuang-Dahuang herb pair inhibiting M1 polarization of alveolar macrophages in prevention and treatment of acute lung injury / 中国药理学通报

ABSTRACT

Aim To investigate the effect of Mahuang-Dahuang(MD)on inhibiting M1 polarization of alveolar macrophages, alleviating inflammatory injury and treating acute lung injury, and the underlying mechanism.Methods Abandoned rats were divided into normal control group(NC), model control group(MC), MD high-dose group(MD-H), medium-dose group(MD-M), low-dose group(MD-L), and DXMS group.Lipopolysaccharide(LPS)was injected intraperitoneally to prepare an acute lung injury(ALI)rat model.After the model was established, different doses of MD were administered by intragastric administration, and the pathological changes of lung tissues were observed; immunohistochemical method was used to detect the expression of alveolar macrophage marker F4/80,F4/80 and CD80, CD80 and IL-6 Co-expression; Flow cytometry was used to detect the content of F4/80 and CD80 in lung tissues; PCR was used to detect the relative expression of IL-6, INOS, TNF-α mRNA in lung tissues; Western blot was used to detect lung tissue CCR2, CCL2, p-p65, P65, p-p38MAPK, p38MAPK protein expression.Results Compared with NC group, rats in MC group had damaged alveolar structure, thickened pulmonary interstitial edema, and infiltrated a large number of inflammatory cells.Among them, the number of macrophages increased significantly, which promoted the increase in the expression of macrophages-related chemokines CCR2 and CCL2.The number and expression of M1 alveolar macrophages in lung tissues increased, the relative expression of M1 alveolar macrophages-related cytokines IL-6, INOS and TNF-α mRNA was up-regulated, and the target protein in the related pathways of alveolar macrophages M1 polarization p-NF-κBp65/NF-κBp65, p-P38MAPK/p38MAPK protein expression was up-regulated.Compared with MC group, the pathological status of lung tissues in MD high, medium, and low dose groups was significantly improved, the number of lung tissue M1 alveolar macrophages decreased, the relative expression of inflammatory factors IL-6, INOS and TNF-α mRNA was down-regulated, and the protein expression of CCR2, CCL2, p-NF-κBp65/ NF-κBp65 and p-P38MAPK/p38MAPK was reduced in lung tissues.Conclusions MD can inhibit the M1 polarization of alveolar macrophages, reduce the activation and release of inflammatory factors, inhibit inflammatory response, and prevent acute lung injury by regulating the expression of related indicators of NF-κB and MAPK signaling pathways.