目的 研究痰热清注射液对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）模型大鼠的治疗作用，同时采用串联质谱标签（tandem mass tags，TMT）定量蛋白质组学探讨其可能的作用机制。方法 Wistar大鼠随机分为对照组、模型组、地塞米松（4 mg/kg）组和痰热清注射液高、中、低剂量（4、2、1 g/kg）组，除对照组外，其余各组制备COPD模型，各给药组ip相应药物。连续给药90 d后，检测肺功能和肺泡灌洗液中细胞因子水平；采用苏木素-伊红和天狼猩红染色观察肺组织病理变化；通过TMT定量蛋白质组学分析对照组、模型组、痰热清注射液中剂量组大鼠肺组织差异蛋白。结果 与对照组比较，模型组大鼠自主活动和精神状态均有所降低，肺功能的顺应性降低（P<0.001），阻力增大（P<0.001），肺组织炎症细胞浸润，肺泡腔扩大，气道壁胶原纤维沉积，表明COPD模型制备成功。与模型组比较，痰热清注射液组大鼠肺功能明显得到改善（P<0.01、0.001），肺泡灌洗液中炎症因子水平明显降低（P<0.05、0.01、0.001）。蛋白组学分析结果显示，痰热清注射液中剂量组和模型组共有61个差异蛋白，差异蛋白与细胞的坏死、凋亡、自噬等信号通路密切相关。结论 痰热清注射液能够明显改善COPD模型大鼠的肺功能等症状，其机制与细胞的坏死、凋亡、自噬等信号通路密切相关。

Objective To study the therapeutic effect of Tanreqing Injection (痰热清注射液) on chronic obstructive pulmonary disease (COPD) model rats, and explore its possible mechanism by tandem mass tags (TMT) quantitative protein omics. Methods Wistar rats were randomly divided into control group, model group, dexamethasone (4 mg/kg) group and Tanreqing Injection high-, medium-and low-dose (4, 2, 1 g/kg) groups. Except for the control group, COPD models were prepared in other groups, and the corresponding drugs were given to each group. After 90 d of continuous administration, lung function and cytokine level in alveolar lavage fluid were detected. Hematoxylin-eosin and picrosirius red staining were used to observe the pathological changes of lung tissue. The differential proteins in lung tissue of rats in control group, model group and Tanreqing Injection medium-dose group were analyzed by TMT quantitative protein omics. Results Compared with control group, the autonomic activity and mental state of rats in model group were decreased, the compliance of lung function was decreased (P < 0.001), the resistance was increased (P < 0.001), inflammatory cells infiltrated in lung tissue, alveolar cavity expanded and collagen fibers deposited in airway wall, which indicated that the COPD model was successfully prepared. Compared with model group, the lung function of rats in Tanreqing Injection group was significantly improved (P < 0.01, 0.001), and the levels of inflammatory factors in alveolar lavage fluid were significantly decreased (P < 0.05, 0.01, 0.001). Proteomic analysis showed that there were 61 differential proteins in Tanreqing Injection medium-dose group and model group, which were closely related to cell necrosis, apoptosis, autophagy and other signal pathways. Conclusion Tanreqing Injection can obviously improve the lung function and other symptoms of COPD model rats, and its mechanism is closely related to signal pathways such as cell necrosis, apoptosis and autophagy.

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国家自然科学基金资助项目（82104502）；中央级公益性科研院所基本科研业务费专项基金资助项目（ZXKT23006，ZZ13-YQ-060，ZXKT21020）；中国中医科学院科技创新工程（CI2021A04615）