Yao Miao-En, Huang Yi, Dong Qing-Qing, Lu Yi, Chen Wei
Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725, South Wanping Road, Xuhui, Shanghai 200032, China.
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China.
Evid Based Complement Alternat Med. 2022 Aug 29;2022:7784148. doi: 10.1155/2022/7784148. eCollection 2022.
The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2 antagonist group, and ALI + CXCR2 antagonist group. We estimated the lung injury by the hematoxylin and eosin staining, the neutrophil extracellular traps (NETs) formations by the immunofluorescence colocalization and enzyme-linked immunosorbent assay (ELISA), and the CXCR2/CXCL2 pathway by the flow cytometry, ELISA, and real-time polymerase chain reaction. We conducted the high-throughput sequencing and enrichment analyses to explore the potential mechanisms. The results showed that the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung injury and inflammatory response but failed to reduce the circulating and lung tissue NETs formation and the blood neutrophil percent. The high-dose RC decoction increased the plasma CXCL2 level, but the RC decoction had no effects on the neutrophilic CXCR2 levels. Under the inhibition of the CXCR2, the middle-dose RC decoction still decreased the lung injury score but as yet had unobvious influence on the NETs formation. Other potential mechanisms of the RC decoction against the ALI involved the pathways of ribosome and coronavirus disease 2019 (COVID-19); the target genes of inflammatory factors, such as , and lncRNAs; and the regulations of the respiratory cilia. In conclusion, the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung inflammatory injury via upregulating the CXCL2/CXCR2 pathway but could not reduce the circulating or lung tissue NETs formation.
急性肺损伤（ALI）会引发严重的肺部疾病，导致高死亡率。人参和赤芍对ALI具有保护和抗炎作用。为探究人参赤芍（RC）水煎剂对ALI的保护作用，我们建立了脂多糖诱导的ALI模型，并将小鼠随机分为七组：对照组、ALI组、高剂量RC组、中剂量RC组、低剂量RC组、中剂量RC组 + CXCR2拮抗剂组和ALI + CXCR2拮抗剂组。我们通过苏木精和伊红染色评估肺损伤，通过免疫荧光共定位和酶联免疫吸附测定（ELISA）评估中性粒细胞胞外陷阱（NETs）形成，通过流式细胞术、ELISA和实时聚合酶链反应评估CXCR2/CXCL2通路。我们进行了高通量测序和富集分析以探究潜在机制。结果显示，RC水煎剂在病理上改善了脂多糖诱导的肺损伤和炎症反应，但未能降低循环和肺组织中NETs的形成以及血液中性粒细胞百分比。高剂量RC水煎剂增加了血浆CXCL2水平，但RC水煎剂对中性粒细胞CXCR2水平无影响。在CXCR2受到抑制的情况下，中剂量RC水煎剂仍降低了肺损伤评分，但对NETs形成的影响尚不明显。RC水煎剂对抗ALI的其他潜在机制涉及核糖体和冠状病毒病2019（COVID - 19）通路；炎症因子的靶基因，如 ，以及长链非编码RNA（lncRNAs）；还有呼吸道纤毛的调节。总之，RC水煎剂通过上调CXCL2/CXCR2通路在病理上改善了脂多糖诱导的肺部炎症损伤，但无法降低循环或肺组织中NETs的形成。
