目的 研究血栓通注射液抗博來霉素誘導(dǎo)肺纖維化模型大鼠的藥效學(xué)。方法 將180只SD大鼠隨機(jī)分為假手術(shù)組、模型組、吡非尼酮（陽性藥，50 mg · kg^-1）組和血栓通注射液低、中、高劑量（注射液原液1、2、4 mL·kg^-1）組，每組30只，采用氣管內(nèi)注射博來霉素方法制備肺纖維化大鼠模型，于造模24 h后各給藥組ip給藥，并分別在造模7、14、28 d取材。觀察大鼠一般狀態(tài)、體質(zhì)量、肺系數(shù)；應(yīng)用DSI/BUXCO監(jiān)測系統(tǒng)檢測肺功能指標(biāo)潮氣量、氣道阻力及肺順應(yīng)性變化；進(jìn)行HE與Masson染色，光鏡下觀察肺組織病理變化；并采用酶聯(lián)免疫吸附法（ELISA）檢測大鼠肺組織中I型膠原（COL-Ⅰ）和纖維黏連蛋白（FN）的水平。結(jié)果 通過對大鼠的一般情況觀察，發(fā)現(xiàn)給予血栓通注射液后，肺纖維化模型大鼠的活動和精神狀態(tài)均有改善。與模型組比較，吡非尼酮組、血栓通注射液組大鼠體質(zhì)量顯著增加（P＜0.01、0.001），大鼠肺系數(shù)顯著降低（P＜0.05、0.01、0.001）。肺功能結(jié)果顯示，與模型組比較，造模7 d時(shí)血栓通注射液中劑量顯著上調(diào)動態(tài)肺順應(yīng)性（P＜0.01）；造模14 d時(shí)血栓通注射液高劑量顯著降低氣道阻力（P＜0.05）和上調(diào)動態(tài)肺順應(yīng)性（P＜0.01）；造模28 d時(shí)吡非尼酮和血栓通注射液中劑量均顯著上調(diào)動態(tài)肺順應(yīng)性（P＜0.01）。HE及Masson結(jié)果顯示，吡非尼酮組、血栓通注射液組的肺纖維化程度明顯輕于模型組。ELISA結(jié)果顯示，與模型組比較，造模7 d時(shí)吡非尼酮組、血栓通注射液高劑量組大鼠肺組織中的FN顯著降低（P＜0.01、0.001），吡非尼酮組COL-Ⅰ水平顯著降低（P＜0.001）；造模14 d時(shí)吡非尼酮組和血栓通注射液中、高劑量組大鼠肺組織中的COL-Ⅰ水平顯著降低（P＜0.05、0.01），吡非尼酮組FN顯著降低（P＜0.05）；造模28 d時(shí)吡非尼酮組和血栓通注射液中、高劑量組大鼠肺組織中的COL-Ⅰ、FN水平顯著降低（P＜0.05、0.01、0.001）。結(jié)論 血栓通注射液可改善肺纖維化模型大鼠肺功能與肺部形態(tài)學(xué)病變，降低肺組織中COL-Ⅰ和FN水平，對肺纖維化大鼠產(chǎn)生保護(hù)作用。

Objective To investigate the effect of Xueshuantong Injection on bleomycin-induced pulmonary fibrosis model rats and its related mechanism. Methods Totally 180 SD rats were randomly divided into sham operation group, model group, pirfenidone group (10 mL·kg^-1), and Xueshuantong Injection low, medium, and high dose (injection stock solution 1, 2, and 4 mL·kg^-1) groups, with 30 rats in each group. The pulmonary fibrosis rat model was prepared by intratracheal injection of bleomycin. Xueshuantong Injection was injected ip in each group at 24 h after modeling,, and the materials were taken on the 7th, 14th, and 28th days of modeling. The general state, body weight and lung coefficient of rats were observed. The changes of tidal volume, airway resistance and lung compliance were detected by DSI/BUXCO monitoring system. HE and Masson staining were performed to observe the pathological changes of lung tissues under light microscope. The levels of type I collagen (COL-Ⅰ) and fibronectin (FN) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Results By observing the general situation of rats, it was found that after giving Xueshuantong Injection, the activity and mental state of pulmonary fibrosis model rats were improved. Compared with the model group, the body mass of rats in the pirfenidone group and Xueshuantong Injection group was significantly increased (P < 0.01, 0.001), and the lung coefficient of rats was lower than that in the model group (P < 0.05, 0.01, 0.001). The results of pulmonary function showed that, compared with the model group, Xueshuantong Injection of medium dose significantly upregulated the dynamic lung compliance at seven days after modeling (P < 0.01). At 14 days after modeling, Xueshuantong Injection of high dose significantly decreased airway resistance (P < 0.05) and upregulated dynamic lung compliance (P < 0.01). At 28 days after modeling, Xueshuantong Injection of medium dose and pirfenidone significantly increased lung compliance (P < 0.01). The results of HE and Masson showed that the degree of pulmonary fibrosis in the pirfenidone group and Xueshuantong Injection group was significantly lighter than that in the model group. ELISA results showed that compared with the model group, FN in lung tissue of rats in pirfenidone group and Xueshuantong Injection high-dose group was significantly decreased at seven days after modeling (P < 0.01, 0.001), and the level of COL-Ⅰ in pirfenidone group was significantly decreased (P < 0.001). At 14 days after modeling, the COL-Ⅰ level in lung tissue of rats in pirfenidone group and Xueshuantong Injection medium and high dose groups was significantly decreased (P < 0.05, 0.01), and FN in pirfenidone group was significantly decreased (P < 0.05). The levels of COL-Ⅰ and FN in lung tissue of rats in pirfenidone group and Xueshuantong Injection medium and high dose groups were significantly decreased at 28 days after modeling (P < 0.01, 0.001). Conclusion Xueshuantong Injection can improve pulmonary function and pulmonary morphological lesions in pulmonary fibrosis model rats, reduce the levels of Col-Ⅰ and FN in lung tissue, and have a protective effect on pulmonary fibrosis rats.

R285.5

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（C12021A04802）；廣西科技基地和人才專項(xiàng)（桂科AD20297068）