Department of Emergency, Huai'an Second People's Hospital, The Affliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
Department of Emergency, Lianshui County People's Hospital, Huai'an, China.
Chem Biol Drug Des. 2024 Jul;104(1):e14579. doi: 10.1111/cbdd.14579.
Sepsis-induced acute lung injury (ALI) is a severe complication of sepsis. Karanjin, a natural flavonoid compound, has been proved to have anti-inflammatory function, but its role in sepsis-stimulated ALI is uncertain. Herein, the effect of karanjin on sepsis-stimulated ALI was investigated. We built a mouse model of lipopolysaccharide (LPS)-stimulated ALI. The histopathological morphology of lung tissues was scrutinized by hematoxylin-eosin (H&E) staining. The lung injury score and lung wet/dry weight ratio were detected. The myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were scrutinized by commercial kits. Murine alveolar lung epithelial (MLE-12) cells were treated with LPS to mimic a cellular model of ALI. The cell viability was scrutinized by the CCK-8 assay. The contents of proinflammatory cytokines were scrutinized by qRT-PCR and ELISA. The TLR4 and MyD88 contents were scrutinized by qRT-PCR and western blotting. Results showed that karanjin alleviated LPS-stimulated ALI in mice by inhibiting lung tissue lesions, edema, and oxidative stress. Moreover, karanjin inhibited LPS-stimulated inflammation and TLR4 pathway activation in mice. However, treatment with GSK1795091, an agonist of TLR4, attenuated the effects of karanjin on LPS-induced ALI. Furthermore, karanjin repressed LPS-stimulated inflammatory response and TLR4 pathway activation in MLE-12 cells. Overexpression of TLR4 attenuated karanjin effects on LPS-stimulated inflammatory responses in MLE-12 cells. In conclusion, karanjin repressed sepsis-stimulated ALI in mice by suppressing the TLR4 pathway.
脓毒症诱导的急性肺损伤（ALI）是脓毒症的严重并发症。卡纳津是一种天然黄酮类化合物，已被证明具有抗炎作用，但它在脓毒症刺激的 ALI 中的作用尚不确定。本文研究了卡纳津对脓毒症刺激的 ALI 的作用。我们构建了脂多糖（LPS）刺激的 ALI 小鼠模型。通过苏木精-伊红（H&E）染色观察肺组织的组织病理学形态。检测肺损伤评分和肺湿/干重比。通过商业试剂盒检测髓过氧化物酶（MPO）活性和丙二醛（MDA）含量。用 LPS 处理鼠肺泡肺上皮（MLE-12）细胞模拟 ALI 的细胞模型。通过 CCK-8 测定法检测细胞活力。通过 qRT-PCR 和 ELISA 检测促炎细胞因子的含量。通过 qRT-PCR 和 Western blot 检测 TLR4 和 MyD88 的含量。结果表明，卡纳津通过抑制肺组织损伤、水肿和氧化应激减轻 LPS 刺激的 ALI。此外，卡纳津抑制了 LPS 刺激的小鼠炎症和 TLR4 途径的激活。然而，TLR4 的激动剂 GSK1795091 的处理减弱了卡纳津对 LPS 诱导的 ALI 的作用。此外，卡纳津抑制了 LPS 刺激的 MLE-12 细胞炎症反应和 TLR4 途径的激活。TLR4 的过表达减弱了卡纳津对 LPS 刺激的 MLE-12 细胞炎症反应的作用。总之，卡纳津通过抑制 TLR4 途径抑制了小鼠脓毒症引起的 ALI。
