目的 探討復(fù)方苦參注射液對(duì)博來霉素誘導(dǎo)肺纖維化模型大鼠的影響及相關(guān)機(jī)制。方法 將120只SD大鼠隨機(jī)分為對(duì)照組、假手術(shù)組、模型組及復(fù)方苦參注射液低、中、高劑量（注射液原液1、2、4 mL·kg^-1）組，每組20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，造模24 h后給藥組ip復(fù)方苦參注射液，第14、28天取材。觀察大鼠一般狀態(tài)、肺系數(shù)、肺功能、肺組織病理變化，并采用酶聯(lián)免疫吸附法（ELISA）檢測(cè)大鼠血清中腫瘤壞死因子-α（TNF-α）和白細(xì)胞介素-1β（IL-1β）的水平，進(jìn)一步檢測(cè)肺組織中羥脯氨酸（HYP）、丙二醛（MDA）和超氧化物歧化酶（SOD）表達(dá)量的變化。結(jié)果 大鼠的一般情況觀察發(fā)現(xiàn)，與假手術(shù)組比較，模型組大鼠食量及飲水量均有所下降，精神萎靡，毛色暗淡發(fā)黃，同時(shí)模型組大鼠出現(xiàn)拱背及口唇、爪甲及尾尖均呈現(xiàn)紫黯現(xiàn)象，部分大鼠出現(xiàn)口鼻出血，呼吸困難現(xiàn)象。給予復(fù)方苦參注射液后，肺纖維化模型大鼠的活動(dòng)和精神狀態(tài)均有改善作用。與假手術(shù)組比較，模型組大鼠體質(zhì)量明顯降低（P<0.01、0.001），肺系數(shù)顯著增加（P<0.001），肺功能指標(biāo)潮氣量下降（P<0.001），氣道阻力升高（P<0.001），動(dòng)態(tài)肺順應(yīng)性降低（P<0.001），肺組織發(fā)生纖維化、炎細(xì)胞浸潤(rùn)等明顯損傷，血清中TNF-α和IL-1β水平顯著升高（P<0.001），肺組織中HYP水平顯著升高（P<0.001），而SOD活性則顯著下降（P<0.001），MDA水平有增加趨勢(shì)。與模型組比較，復(fù)方苦參注射液低、中劑量組大鼠體質(zhì)量顯著增加（P<0.05、0.001），大鼠肺系數(shù)顯著降低（P<0.05、0.001），潮氣量顯著上調(diào)（P<0.001），氣道阻力顯著降低（P<0.01、0.001），動(dòng)態(tài)肺順應(yīng)性顯著上調(diào)（P<0.01、0.001），大鼠肺組織纖維化程度明顯減輕，血清中TNF-α水平降低（P<0.01、0.001），肺組織中HYP含量顯著降低（P<0.01），SOD活性則顯著升高（P<0.05、0.01、0.001），MDA有下調(diào)趨勢(shì)，但差異不顯著。結(jié)論 復(fù)方苦參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，降低血清中TNF-α水平，以及下調(diào)肺組織中HYP含量與提高SOD活性，減輕炎性反應(yīng)并增加抗氧化能力，對(duì)肺纖維化大鼠產(chǎn)生保護(hù)作用。

Objective To investigate the effect of Compound Kushen Injection on bleomycin induced pulmonary fibrosis in rats. Methods 120 SD rats were randomly divided into control group, Sham operation group, model group, low-, middle- and high-dose (1, 2, 4 mL·kg^-1) groups of Compound Kushen Injection, with 20 rats in each group. The rat model of pulmonary fibrosis was established by exposed injection of bleomycin into trachea. Compound Kushen Injection was intraperitoneally injected 24 h after the model was established. The rats were killed on the 14th and 28th day. The general state, lung coefficient, lung function and pathological changes of lung tissue were observed. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of hydroxyproline (HYP), malondialdehyde (MDA) and superoxide dismutase (SOD) in lung tissue were detected. Result Through the observation of the general situation of rats, it is found that compared with the sham operation group, the food and water consumption of the model group decreased, the spirit wasdepressed, and the hair color was dim and yellow. At the same time, the model group rats had arched back, and the lips, claw nails and tail tips were purple. Some rats had mouth and nose bleeding and dyspnea. After administration of Compound Kushen Injection, the activity and mental state of pulmonary fibrosis model rats were improved. Compared with the Sham operation group, the body mass of the model group decreased significantly (P < 0.01, 0.001), the lung coefficient increased significantly (P < 0.001), the tidal volume of pulmonary function index decreased (P < 0.001), the airway resistance increased (P < 0.001), the dynamic lung compliance decreased (P < 0.001), and the lung tissue suffered obvious injury such as fibrosis and inflammatory cell infiltration, the levels of TNF-α and IL-1β in serum increased significantly (P < 0.001), the level of HYP in lung tissue increased significantly (P < 0.001), while the activity of SOD decreased significantly (P < 0.001), and the level of MDA increased. Compared with the model group, the body mass of rats in the low- and medium-dose groups of Compound Kushen Injection increased significantly (P < 0.05, 0.001), the lung coefficient decreased significantly (P < 0.05, 0.001), the tidal volume increased significantly (P < 0.001), the airway resistance decreased significantly (P < 0.01, 0.001) and the dynamic lung compliance increased significantly (P < 0.01, 0.001), and the degree of pulmonary fibrosis decreased significantly, the level of TNF-α in serum decreased (P < 0.01, 0.001), the content of HYP in lung tissue decreased significantly (P < 0.01), and the activity of SOD increased significantly (P < 0.05, 0.01, 0.001). MDA decreased, but the difference was not significant. Conclusion Compound Kushen Injection can improve pulmonary function and pulmonary morphological changes, and reduce serum TNF-α in rats with pulmonary fibrosis, and down regulate the content of HYP in lung tissue, increase SOD activity, reduce inflammatory reaction and increase antioxidant capacity, which has a protective effect on pulmonary fibrosis rats.

R285.5

“十三五”國(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2018YFC1602104）；中國(guó)中醫(yī)科學(xué)院中藥研究所自主選題項(xiàng)目（ZXKT20015）