目的 探索补肺活血胶囊治疗特发性肺纤维化的作用及其机制。方法 将60只C57BL/6J雄性小鼠分为对照组、模型组、吡非尼酮组及补肺活血胶囊高、低剂量组，每组各12只。除对照组外，其余各组小鼠气管滴注博来霉素建立肺纤维化模型。造模后第1天开始干预治疗，补肺活血胶囊低、高剂量组分别ig 315、630 mg/(kg∙d)的补肺活血胶囊溶液，吡非尼酮组ig吡非尼酮200 mg/(kg∙d)，对照组、模型组ig等剂量生理盐水。连续给药28 d后取材，收集小鼠的肺组织，分别运用苏木精–伊红染色（HE）和马松（Masson）法观察小鼠的肺组织病理学变化，酶联免疫吸附法（ELISA）检测肺组织羟脯氨酸（HYP）含量，实时荧光定量（qRT-PCR）法检测肺组织Ⅰ型胶原蛋白（COL-I）、纤连蛋白1（Fn1）、α-平滑肌肌动蛋白（α-SMA）mRNA相对表达水平，免疫组化法检测肺组织磷酸化的磷脂酰肌醇-3-激酶（p-PI3K）和磷酸化的蛋白激酶B（p-Akt）蛋白的表达水平。结果 与对照组比较，模型组小鼠肺组织结构明显被破坏、炎症细胞渗出及胶原纤维沉积增多，肺组织中HYP含量明显升高，COL-I、Fn1、α-SMA mRNA相对表达量均明显升高，p-PI3K和p-Akt蛋白的表达量显著升高（P＜0.01）；与模型组相比，补肺活血胶囊高剂量组、吡非尼酮组小鼠肺组织结构改善明显、炎症细胞渗出以及胶原纤维沉积明显减少，肺组织中HYP含量明显降低，COL-Ⅰ、Fn1、α-SMA mRNA相对表达量均明显降低，p-PI3K和p-Akt蛋白的表达量显著降低（P＜0.01）。结论 补肺活血胶囊具有抗纤维化的作用，可能与PI3K/Akt信号通路有关。

Objective To explore the effect and mechanism of Bufei Huoxue Capsule in treatment of idiopathic pulmonary fibrosis. Methods 60 C57BL/6J male mice were divided into control group (n=12), model group (n=12), pirfenidone group (n=12), Bufei Huoxue Capsule high dose group (n=12) and Bufei Huoxue Capsules low dose group (n=12). Except the control group, the pulmonary fibrosis model was established by intratracheal instillation of bleomycin in other groups. Intervention treatment began on the first day after the establishment of the model. The low and high dose groups of Bufei Huoxue Capsules were given 315 and 630 mg/(kg·d) Bufei Huoxue Capsules solution, respectively. Pirfenidone group were ig pirfenidone 200 mg/(kg∙d). The control group and model group were given the same dose of normal saline. After 28 d of continuous administration, the lung tissues of mice were collected, the pathological changes of lung tissues were observed by hematoxylin-eosin staining (HE) and Masson pine (Masson) method, and the content of hydroxyproline (HYP) in lung tissue was detected by enzyme-linked immunosorbent assay (ELISA). The relative expression levels of collagen Ⅰ (COL-Ⅰ), fibronectin 1 (Fn1) and α-smooth muscle actin (α-SMA) mRNA in lung tissue were detected by real-time fluorescence quantification (qRT-PCR). The expression levels of phosphatidylinositol-3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) in lung tissue were detected by immunohistochemistry. Results Compared with the control group, the lung tissue structure of the model group was obviously destroyed, the exudation of inflammatory cells and the deposition of collagen fibers increased, the content of HYP in the lung tissue, the relative expression of COL-Ⅰ, Fn1, α-SMA mRNA, and the expression of p-PI3K and p-Akt protein increased significantly in the model group (P < 0.01). Compared with the model group, the lung tissue structure of the mice in the high dose Bufei Huoxue Capsules group and the pifenidone group were significantly improved, the inflammatory cell exudation and collagen fiber deposition were significantly decreased, the content of HYP in the lung tissue was significantly decreased, the relative expressions of COL-Ⅰ, Fn1, α-SMA mRNA, and the expression of p-PI3K and p-Akt protein were significantly decreased (P < 0.01). Conclusion Bufei Huoxue Capsules has the effect of anti-fibrosis, which may be related to PI3K/Akt signal pathway.

高层次公共卫生技术人才培养建设项目计划项目（学科带头人-01-16）