基于NLRP3炎症信号通路的清瘟败毒汤治疗急性肺损伤的机制研究
Mechanistic Study on the Treatment of Acute Lung Injury with Qingwen Baidu Decoction based on NLRP3 Inflammasome Signaling Pathway.
摘要(中文译文)
清瘟败毒饮（QWBD）作为经典中药方剂，在治疗急性肺损伤（ALI）方面已显示出临床疗效。然而，其保护作用的具体机制尚不清楚。通过高效液相色谱法（HPLC）鉴定了QWBD的主要生物活性成分。建立脂多糖（LPS）诱导的体内和体外炎症模型以评估治疗效果。通过肺湿干重比（W/D）评估肺水肿严重程度，同时通过苏木精-伊红（H&E）染色和透射电子显微镜（TEM）检查组织病理学改变。定量检测髓过氧化物酶（MPO）活性和炎性细胞因子水平以确定中性粒细胞活化和炎症反应。通过针对NLRP3炎症小体通路的免疫组织化学（IHC）、免疫荧光（IF）和蛋白质印迹法（WB）获得机制性见解。HPLC分析鉴定了QWBD中四种主要生物活性成分。治疗显著减轻了ALI大鼠的肺水肿，改善了肺泡结构损伤，并恢复了II型肺泡上皮细胞的超微结构完整性。与LPS处理组相比，QWBD显著抑制了MPO活性并降低了促炎细胞因子水平。IHC/IF显示对半胱氨酸天冬氨酸蛋白酶-1（Caspase-1）和NOD样受体蛋白3（NLRP3）表达的有效抑制，而WB证实了NLRP3炎症小体相关蛋白的下调。QWBD通过抑制NLRP3炎症小体活化及上游调控因子，从而减弱促炎细胞因子的成熟，从而缓解ALI。其多成分组成赋予了优于单靶点药物的优势，同时可能避免与地塞米松相关的广泛免疫抑制。其治疗潜力的临床验证仍有必要。QWBD通过抑制NLRP3炎症小体发挥抗ALI保护作用，有望成为炎症性肺部疾病的多靶点治疗药物。
Abstract
Qingwen Baidu Decoction (QWBD), a classical traditional Chinese medicine formula, has demonstrated clinical efficacy in managing acute lung injury (ALI). However, the precise mechanisms underlying its protective effects remain poorly characterized. Major bioactive constituents of QWBD were identified through high-performance liquid chromatography (HPLC). Lipopolysaccharide (LPS)-induced in vivo and in vitro inflammatory models were established to evaluate therapeutic outcomes. Pulmonary edema severity was assessed via lung wet-to-dry weight ratio (W/D), while histopathological alterations were examined through hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Myeloperoxidase (MPO) activity and inflammatory cytokine levels were quantified to determine neutrophil activation and inflammatory responses. Mechanistic insights were obtained through immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) targeting the NLRP3 inflammasome pathway. HPLC analysis identified four principal bioactive components in QWBD. Treatment significantly attenuated pulmonary edema, ameliorated alveolar structural damage, and restored ultrastructural integrity of type II pneumocytes in ALI rats. QWBD significantly suppressed MPO activity and reduced pro-inflammatory cytokine levels compared to the LPS-treated group. IHC/IF revealed potent inhibition of cysteine-aspartic protease-1 (Caspase-1) and NOD-like receptor protein 3 (NLRP3) expression, while WB confirmed downregulation of NLRP3 inflammasome- associated proteins. QWBD alleviates ALI by inhibiting NLRP3 inflammasome activation and upstream regulators, thereby attenuating pro-inflammatory cytokine maturation. Its multi-component composition confers advantages over single-target agents while potentially avoiding the broad immunosuppression associated with dexamethasone. Clinical validation of its therapeutic potential remains warranted. QWBD protects against ALI by implying NLRP3 inflammasome suppression, demonstrating promise as a multi-targeted therapy for inflammatory lung disorders.
如何引用
AMA
Jinhui Feng, Xiangzheng Mao, Wenting Wang, Ke Yang, Sha Li, Bin Wang, et al. Mechanistic Study on the Treatment of Acute Lung Injury with Qingwen Baidu Decoction based on NLRP3 Inflammasome Signaling Pathway.. Combinatorial chemistry & high throughput screening. 2026; doi:10.2174/0113862073387330251111021249.
APA
Jinhui Feng, Xiangzheng Mao, Wenting Wang, Ke Yang, Sha Li, Bin Wang, et al (2026). Mechanistic Study on the Treatment of Acute Lung Injury with Qingwen Baidu Decoction based on NLRP3 Inflammasome Signaling Pathway.. Combinatorial chemistry & high throughput screening. https://doi.org/10.2174/0113862073387330251111021249
GB/T 7714
Jinhui Feng, Xiangzheng Mao, Wenting Wang, Ke Yang, Sha Li, Bin Wang, et al. Mechanistic Study on the Treatment of Acute Lung Injury with Qingwen Baidu Decoction based on NLRP3 Inflammasome Signaling Pathway.[J]. Combinatorial chemistry & high throughput screening, 2026 doi:10.2174/0113862073387330251111021249.
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