目的 观察宣肺化瘀方对肺纤维化大鼠肺组织TGF-β1/Smad2表达的影响。方法 将健康雄性Wistar大鼠（SPF级）60只，随机分成6组，对照组、模型组、醋酸泼尼松（0.167 mg/kg）组及宣肺化瘀方高、中、低剂量（14.38、7.19、3.60 g/kg）组，每组10只。经鼻滴入博莱霉素7 μg/g（150μL）建立肺纤维化动物模型。各给药组于造模8 h后开始分别ig醋酸泼尼松或宣肺化瘀方，每日1次。各组大鼠在造模28 d后取材。对肺组织行HE染色和天狼星红染色，光镜下观察肺泡炎和肺纤维化改变；采用碱性水解法测定肺组织中羟脯氨酸（Hyp）的量；应用免疫组织化学法测定大鼠肺组织α-平滑肌肌动蛋白（α-SMA）、Smad4、Smad7表达；应用Western blotting方法检测转化生长因子β Ⅱ型受体（TGF-β RⅡ）、Smad2、p-Smad2、Smad7的蛋白表达水平。结果 模型组肺泡结构严重破坏，肺间质增生，炎细胞浸润和胶原纤维增生。与对照组比较，模型组Hyp水平、胶原阳性染色面积比值明显升高；与模型组相比，宣肺化瘀方3个剂量组和醋酸泼尼松组肺泡间隔胶原纤维表达明显减少，Hyp的量显著下降，其中，宣肺化瘀方高剂量组比低、中剂量组胶原纤维表达更少，Hyp的量更低。宣肺化瘀方组与模型组相比，TGF-β RⅡ、Smad2、p-Smad2、Smad4、α-SMA蛋白含量显著降低，而Smad7蛋白表达明显升高。结论 宣肺化瘀方能有效地防治肺纤维化，其作用机制可能是通过调控TGF-β/Smad信号通路，抑制α-SMA的过度表达，进而减少胶原纤维的形成。

Objective To investigate the effects of Xuanfei Huayu Formula (XFHY) on the expression of TGF-β1/Smad2 in pulmonary fibrosis rats. Methods Sixty male SPF Wistar rats were randomly divided into six groups:negative control group (group A), pulmonary fibrosis model group (group B), prednisone positive control group (group C, 0.167 mg/kg), the high doses of XFHY groups (group D, 14.38 g/kg), the medium doses of XFHY groups (group E, 7.19 g/kg), and the low doses of XFHY groups (group F, 3.60 g/kg) with ten rats in each group. The pulmonary fibrosis model was established by nasal instillation of bleomycin 7 μg/g (150 μL); In 8 h after the modle establishment, the rats in C, D, E, and F groups were respectively treated with prednisone acetate or XFHY once daily. Negative control group (group A) and model group (group B) were given equal volume physiological saline. The rats in different groups were executed 28 d after modeling for sampling. The HE and sirius red staining were used to observe alveolitis even pulmonary fibrosis changes in lung tissue under the microscope; The alkaline hydrolysis method was adopted to determine the content of hydroxyproline (Hyp) in lung tissue; The immunohistochemical method was used to determine the expression of alpha-SMA, Smad4, and Smad7 in rat lung tissues. The expression levels of TGF-β RⅡ, Smad2, p-Smad2, and Smad7 proteins were detected by Western blotting. Results The alveolar structure of the model group was severely damaged, and the interstitial hyperplasia, inflammatory cell infiltration, and collagen fibrosis were observed. Compared with the negative control group, the content of hydroxyproline and collagen staining was significantly increased in the model group. Compared with the model group, the expression of collagen fibers in the alveolar interval of three-dose group and prednisolone acetate group was significantly reduced, and the content of hydroxyproline was decreased significantly. Among them, the collagen fiber expression in XFHY high-dose group was less than XFHY low-and medium-dose group, and the hydroxyproline content was much lower. The above results showed that XFHY had a certain dose-effect relationship with the efficacy of pulmonary fibrosis. On this basis, the mechanism of the action of XFHY continues to it should be further explored. It was found that the protein content of TGF-β RⅡ, Smad2, p-Smad2, Smad4, and α-SMA were decreased significantly, while the expression of Smad7 was higher in the XFHY group compared with the model group. Conclusion XFHY can effectively prevent and treat pulmonary fibrosis, and its mechanism may relate to inhibit the over-expression of the α-SMA by regulating the TGF-β/Smad signaling pathway, thereby reducing the formation of collagen fibers.

国家自然科学基金资助项目（81001491）；上海市自然科学基金项目（15ZR1441100）；经方理论应用研究中心（A1-Z183020110）；上海市“中医学”一流学科科研创新基金项目；上海中医药大学院院合作项目