目的 探討霧化吸入粉防己堿對博來霉素誘導(dǎo)肺纖維化大鼠模型的藥效作用。方法 將100只SD大鼠隨機(jī)分為對照組、假手術(shù)組、模型組、粉防己堿（5 mg·mL^-1）霧化10、30 min（單次實(shí)際給藥劑量為0.072、0.220 mg·^kg-1）組，每組10只，并采用氣管注入博來霉素方法制備大鼠肺纖維化模型，造模24 h后霧化給藥。連續(xù)給藥第14、28 d，觀察大鼠肺系數(shù)、肺功能，HE染色后觀察肺組織病理，Masson染色后觀察膠原纖維變化，天狼星紅染色檢測大鼠肺組織中I型與III型膠原纖維；并采用Western blotting檢測肺組織中波形蛋白（Vimentin）、α-平滑肌肌動(dòng)蛋白（α-SMA）和轉(zhuǎn)化生長因子-β1（TGF-β1）表達(dá)；酶聯(lián)免疫吸附（ELISA）法檢測大鼠肺組織中羥脯氨酸（HYP）和纖連蛋白（FN）含量。結(jié)果 粉防己堿霧化后中位粒徑為2.98 μm；給藥28 d時(shí)效果更優(yōu)，與模型組比較，霧化30 min組的氣道阻力顯著降低（P＜0.05），肺順應(yīng)性顯著升高（P＜0.05），肺系數(shù)顯著降低（P＜0.05）；肺泡炎癥評分、肺纖維化評分顯著降低（P＜0.05），I型和III型膠原纖維明顯減少； Vimentin和TGF-β 1的表達(dá)顯著下調(diào)（P＜0.01）；顯著下調(diào)HYP和FN的水平（P＜0.05）。結(jié)論 霧化吸入粉防己堿具有抗大鼠肺纖維化作用，其中霧化給藥28 d效果更優(yōu)。

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.

國家自然科學(xué)基金青年項(xiàng)目（82204740）；中央級公益性科研院所基本科研業(yè)務(wù)費(fèi)專項(xiàng)資金資助（ZXKT22045）；中國中醫(yī)科學(xué)院中藥研究所中藥藥理創(chuàng)新團(tuán)隊(duì)項(xiàng)目（CI2021B015）；中國中醫(yī)科學(xué)院科技創(chuàng)新工程重大攻關(guān)項(xiàng)目（CI2021A04615）