<br>巴马汀通过 NAMPT/TLR2/CCR1 信号传导抑制 M1 表型巨噬细胞极化，减轻脂多糖引起的急性肺损伤,Journal of Agricultural and Food Chemistry

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巴马汀通过 NAMPT/TLR2/CCR1 信号传导抑制 M1 表型巨噬细胞极化，减轻脂多糖引起的急性肺损伤
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-04-15 , DOI: 10.1021/acs.jafc.3c05597
Lei Wang ₁ , Jinchun Wang ₁ , Lei Han ₁ , Tong Chen ₂

Affiliation

目前的工作是研究巴马汀（PAL）对脂多糖（LPS）引起的急性肺损伤（ALI）的潜在机制。进行了网络药理学和生物信息学分析。小鼠用 PAL 进行胃内治疗，并用 LPS 进行气管内刺激。 LPS诱导的RAW264.7细胞用于体外模型。检查 MPO 活性、W/D 比、中性粒细胞、BALF 中的细胞总数和组织病理学变化。采用ELISA法检测血清、BALF及上清液中TNF-α、IL-1β、IL-6、IL-18、IL-4、IL-10的水平。采用PCR、WB、免疫荧光法检测iNOS、CD68、Arg1、Ym1、CD206 mRNA表达量以及NAMPT、TLR2、CCR1、NLRP3炎症小体蛋白表达量。使用NAMPT抑制剂FK866、TLR2抑制剂C29、CCR1抑制剂BX471、NAMPT过表达(OE)质粒和TLR2-OE质粒进行机制研究。结果，PAL 缓解了 ALI 的症状。在 LPS 诱导的小鼠和 RAW264.7 细胞中，PAL 抑制 M1 表型指数并促进 M2 表型指数。 PAL 还抑制 NAMPT、TLR2、CCR1 和 NLRP3 炎性体的表达。 FK866、NAMPT-OE质粒、C29、TLR2-OE质粒和BX471处理证明PAL通过NAMPT/TLR2/CCR1发挥作用。分子对接表明PAL可能与NAMPT结合。总之，PAL 通过 NAMPT/TLR2/CCR1 信号传导抑制 M1 表型巨噬细胞极化，从而改善 LPS 诱导的 ALI。

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Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling

The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1β, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.

更新日期：2024-04-15

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