摘要
目的探讨复方苦参注射液对博来霉素诱导肺纤维化模型大鼠的影响及相关机制。方法将120只SD大鼠随机分为对照组、假手术组、模型组及复方苦参注射液低、中、高剂量(注射液原液1、2、4 mL·kg^(−1))组,每组20只,采用气管内注射博来霉素方法制备肺纤维化大鼠模型,造模24 h后给药组ip复方苦参注射液,第14、28天取材。观察大鼠一般状态、肺系数、肺功能、肺组织病理变化,并采用酶联免疫吸附法(ELISA)检测大鼠血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平,进一步检测肺组织中羟脯氨酸(HYP)、丙二醛(MDA)和超氧化物歧化酶(SOD)表达量的变化。结果大鼠的一般情况观察发现,与假手术组比较,模型组大鼠食量及饮水量均有所下降,精神萎靡,毛色暗淡发黄,同时模型组大鼠出现拱背及口唇、爪甲及尾尖均呈现紫黯现象,部分大鼠出现口鼻出血,呼吸困难现象。给予复方苦参注射液后,肺纤维化模型大鼠的活动和精神状态均有改善作用。与假手术组比较,模型组大鼠体质量明显降低(P<0.01、0.001),肺系数显著增加(P<0.001),肺功能指标潮气量下降(P<0.001),气道阻力升高(P<0.001),动态肺顺应性降低(P<0.001),肺组织发生纤维化、炎细胞浸润等明显损伤,血清中TNF-α和IL-1β水平显著升高(P<0.001),肺组织中HYP水平显著升高(P<0.001),而SOD活性则显著下降(P<0.001),MDA水平有增加趋势。与模型组比较,复方苦参注射液低、中剂量组大鼠体质量显著增加(P<0.05、0.001),大鼠肺系数显著降低(P<0.05、0.001),潮气量显著上调(P<0.001),气道阻力显著降低(P<0.01、0.001),动态肺顺应性显著上调(P<0.01、0.001),大鼠肺组织纤维化程度明显减轻,血清中TNF-α水平降低(P<0.01、0.001),肺组织中HYP含量显著降低(P<0.01),SOD活性则显著升高(P<0.05、0.01、0.001),MDA有下调趋势,但差异不显著。结论复方苦参注射液可改善肺纤维化模型大鼠肺功能与肺部形态学病变,降低血清中TNF-α水平,以及下调肺组织中HYP含量与提高SOD活性,减轻炎性反应并增加抗氧化能力,对肺纤维化大鼠产生保护作用。
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 was depressed,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-αand IL-1βin 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-αin 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-αin 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.
作者
李晗
高云航
宋玲
陈腾飞
侯红平
叶祖光
张广平
LI Han;GAO Yunhang;SONG Ling;CHEN Tengfei;HOU Hongping;YE Zuguang;ZHANG Guangping(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《药物评价研究》
CAS
2022年第2期241-250,共10页
Drug Evaluation Research
基金
“十三五”国家重点研发计划项目(2018YFC1602104)
中国中医科学院中药研究所自主选题项目(ZXKT20015)。
关键词
复方苦参注射液
肺纤维化
博来霉素
肺功能
炎性反应
氧化应激
Compound Kushen Injection
pulmonary fibrosis
bleomycin
pulmonary function
inflammatory reaction
oxidative stress
