State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, School of Pharmaceutical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
School of Food and Bioengineering, Xihua University, Chengdu, China.
Front Immunol. 2023 Oct 25;14:1285550. doi: 10.3389/fimmu.2023.1285550. eCollection 2023.
Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-B) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-B signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-B signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-B signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.
急性肺损伤（ALI）是一种常见疾病，特别是在 COVID-19 大流行期间，其特征是呼吸急促、氧难治性发绀、肺顺应性降低和肺泡弥漫性浸润导致呼吸功能不全突然发作。TLR4/NF-κB 信号轴和 NOD、LRR 和富含吡咯烷结构域蛋白 3（NLRP3）炎症小体激活的活性增加与 ALI 的发病机制有关，这已得到充分证实。由于 ALI 对人类健康构成巨大挑战，因此迫切需要通过治疗干预来解决这一问题。秦艽升葛口服液（QHSG）是一种中药配方，临床上用于有效治疗各种肺部疾病，包括 ALI，其作用机制尚不清楚。在本研究中，通过脂多糖（LPS）诱导的 ALI 大鼠模型，发现 QHSG 通过减轻病理特征、逆转白细胞谱的改变以及通过下调 TLR4/NF-κB 信号级联和抑制 NLRP3 炎症小体激活来抑制炎症细胞因子的产生，从而改善 ALI。在 LPS 刺激的 RAW264.7 小鼠巨噬细胞中，发现 QHSG 通过减弱 TLR4/NF-κB 信号通路活性和减弱 NLRP3 炎症小体激活来阻止炎症细胞因子的产生。综上所述，QHSG 可能通过减轻 TLR4/NF-κB 信号级联和抑制 NLRP3 炎症小体激活来解决急性肺损伤，从而发挥其抗炎和免疫调节作用。我们的研究结果为 QHSG 的作用机制提供了新的见解，并为临床实践中用 QHSG 治疗急性肺损伤提供了机制基础。
