目的 探索補肺活血膠囊治療特發(fā)性肺纖維化的作用及其機制。方法 將60只C57BL/6J雄性小鼠分為對照組、模型組、吡非尼酮組及補肺活血膠囊高、低劑量組，每組各12只。除對照組外，其余各組小鼠氣管滴注博來霉素建立肺纖維化模型。造模后第1天開始干預治療，補肺活血膠囊低、高劑量組分別ig 315、630 mg/(kg∙d)的補肺活血膠囊溶液，吡非尼酮組ig吡非尼酮200 mg/(kg∙d)，對照組、模型組ig等劑量生理鹽水。連續(xù)給藥28 d后取材，收集小鼠的肺組織，分別運用蘇木精–伊紅染色（HE）和馬松（Masson）法觀察小鼠的肺組織病理學變化，酶聯(lián)免疫吸附法（ELISA）檢測肺組織羥脯氨酸（HYP）含量，實時熒光定量（qRT-PCR）法檢測肺組織Ⅰ型膠原蛋白（COL-I）、纖連蛋白1（Fn1）、α-平滑肌肌動蛋白（α-SMA）mRNA相對表達水平，免疫組化法檢測肺組織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）蛋白的表達水平。結(jié)果 與對照組比較，模型組小鼠肺組織結(jié)構(gòu)明顯被破壞、炎癥細胞滲出及膠原纖維沉積增多，肺組織中HYP含量明顯升高，COL-I、Fn1、α-SMA mRNA相對表達量均明顯升高，p-PI3K和p-Akt蛋白的表達量顯著升高（P＜0.01）；與模型組相比，補肺活血膠囊高劑量組、吡非尼酮組小鼠肺組織結(jié)構(gòu)改善明顯、炎癥細胞滲出以及膠原纖維沉積明顯減少，肺組織中HYP含量明顯降低，COL-Ⅰ、Fn1、α-SMA mRNA相對表達量均明顯降低，p-PI3K和p-Akt蛋白的表達量顯著降低（P＜0.01）。結(jié)論 補肺活血膠囊具有抗纖維化的作用，可能與PI3K/Akt信號通路有關(guān)。

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.

高層次公共衛(wèi)生技術(shù)人才培養(yǎng)建設(shè)項目計劃項目（學科帶頭人-01-16）