目的 探讨雾化吸入粉防己碱对博来霉素诱导肺纤维化大鼠模型的药效作用。方法 将100只SD大鼠随机分为对照组、假手术组、模型组、粉防己碱（5 mg·mL^-1）雾化10、30 min（单次实际给药剂量为0.072、0.220 mg·^kg-1）组，每组10只，并采用气管注入博来霉素方法制备大鼠肺纤维化模型，造模24 h后雾化给药。连续给药第14、28 d，观察大鼠肺系数、肺功能，HE染色后观察肺组织病理，Masson染色后观察胶原纤维变化，天狼星红染色检测大鼠肺组织中I型与III型胶原纤维；并采用Western blotting检测肺组织中波形蛋白（Vimentin）、α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β1（TGF-β1）表达；酶联免疫吸附（ELISA）法检测大鼠肺组织中羟脯氨酸（HYP）和纤连蛋白（FN）含量。结果 粉防己碱雾化后中位粒径为2.98 μm；给药28 d时效果更优，与模型组比较，雾化30 min组的气道阻力显著降低（P＜0.05），肺顺应性显著升高（P＜0.05），肺系数显著降低（P＜0.05）；肺泡炎症评分、肺纤维化评分显著降低（P＜0.05），I型和III型胶原纤维明显减少； Vimentin和TGF-β 1的表达显著下调（P＜0.01）；显著下调HYP和FN的水平（P＜0.05）。结论 雾化吸入粉防己碱具有抗大鼠肺纤维化作用，其中雾化给药28 d效果更优。

Objective To explore the pharmacological effect of atomized tetrandrine on a rat model of pulmonary fibrosis induced by bleomycin.Methods Totally 100 SD rats were randomly divided into blank group, sham operation group, 10 and 30 min atomization of tetrandrine (5 mg·mL^-1) group, with 10 rats in each group. A rat pulmonary fibrosis model was prepared by tracheal injection of bleomycin. The model was established for 24 hours and atomized, and samples were taken on the 14th and 28th days of administration. Determined the lung coefficient, lung function, lung tissue pathology, and collagen fiber changes in rats. Vimentin, α -smooth muscle actin (α - SMA) and transforming growth factors-β1(TGF-β1) expression in lung tissue was detected by Western blotting. Enzyme linked immunosorbent assay (ELISA) for detecting hydroxyproline (HYP) and fibronectin (FN) levels in rat lung tissue. Results The median particle size of powder tetrandrine after atomization is 2.98 μm. The effect was better after 28 days of administration. Compared with the model group, the 30 min atomization of tetrandrine group showed a significant decrease in airway resistance (P＜0.05), a significant increase in lung compliance (P＜0.05), and a significant decrease in lung coefficient (P＜0.05). The scores of alveolar inflammation and pulmonary fibrosis were significantly reduced (P＜0.05), and the number of type I and III collagen fibers was significantly reduced. The expression of Vimentin and TGF- β1 was significantly downregulated (P＜0.01). The levels of HYP and FN were significantly downregulated (P＜0.05). Conclusion Atomized inhalation of tetrandrine has an anti pulmonary fibrosis effect in rats, with a better effect after 28 days of administration.

国家自然科学基金青年项目（82204740）；中央级公益性科研院所基本科研业务费专项资金资助（ZXKT22045）；中国中医科学院中药研究所中药药理创新团队项目（CI2021B015）；中国中医科学院科技创新工程重大攻关项目（CI2021A04615）