丹参通络解毒汤对博莱霉素诱导的肺纤维化小鼠肿瘤坏死因子样弱凋亡诱导因子/成纤维细胞生长因子诱导14通路的影响  

Effect of Danshen Tongluo Jiedu decoction on tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14 pathway in mice with pulmonary fibrosis induced by bleomycin

作　　者：王中超[1] 何延忠[1] 赵栋梁[1] 周淼[1] WANG Zhongchao;HE Yanzhong;ZHAO Dongliang;ZHOU Miao(Department of Pulmonary Diseases,the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450003,Henan Province,China)

机构地区：[1]河南中医药大学第三附属医院肺病科,河南郑州450003

出　　处：《新乡医学院学报》2021年第12期1101-1112,共12页Journal of Xinxiang Medical University

基　　金：国家中医药管理局国家中医临床研究基地业务建设科研专项课题(编号:JDZX2015158)。

摘　　要：目的观察丹参通络解毒汤对博莱霉素诱导的肺纤维化小鼠肿瘤坏死因子样弱凋亡诱导因子(TWEAK)/成纤维细胞生长因子诱导14(Fn14)通路的影响,探讨其对小鼠肺纤维化的影响及机制。方法取C57B/L小鼠50只随机分为空白组、模型组、1,25-二羟维生素D_(3)[1,25(OH)_(2)D_(3)]组、丹参通络解毒汤组、丹参通络解毒汤+TWEAK/Fn14抑制剂PDL192组。模型组、1,25(OH)_(2)D_(3)组、丹参通络解毒汤组、丹参通络解毒汤+PDL192组小鼠气管内注射博莱霉素建立小鼠肺纤维化模型。造模成功后,空白组和模型组小鼠每日灌胃生理盐水10 mL·kg^(-1);1,25(OH)_(2)D_(3)组小鼠每日经腹腔注射1,25(OH)_(2)D_(3)5μg·kg^(-1);丹参通络解毒汤组小鼠每日灌胃丹参通络解毒汤汤剂0.039 mL·g^(-1)(按成人60 kg体质量计算,相当于生药15.65 g·kg^(-1));丹参通络解毒汤+PDL192组小鼠每日灌胃丹参通络解毒汤汤剂0.039 mL·g^(-1),并经腹腔注射PDL1923 mg·kg^(-1);各组小鼠均每日给药1次,连续给药28 d;末次给药后12 h测体质量,然后经腹腔注射戊巴比妥钠进行麻醉、固定,采集肺支气管肺泡灌洗液(BALF),开胸取肺组织,测肺质量,计算小鼠肺系数。采用酶标仪检测5组小鼠BALF中白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素4(IL-4)水平。苏木精-伊红染色和Masson三色法染色法观察5组小鼠肺组织病理学变化。实时荧光定量聚合酶链式反应法检测5组小鼠肺组织TWEAK、Fn14、转化生长因子β_(1)(TGF-β_(1))mRNA表达。Western blot法检测5组小鼠肺组织炎症细胞因子TNF-α、IL-1β、细胞间黏附分子(ICAM-1)、血管细胞黏附分子1(VCAM-1)及肺组织TWEAK/Fn14通路因子TWEAK、Fn14、TGF-β_(1)、α-平滑肌肌动蛋白(α-SMA)、母亲信号蛋白同源物3(Smad3)、磷酸化母亲信号蛋白同源物3(p-Smad3)、信号传导和转录激活因子3(STAT3)、酪氨酸磷酸化STAT3(p-STAT3)蛋白相对表达量。结果空�Objective To observe the effects of Danshen Tongluo Jiedu decoction on tumor necrosis factor-like weak inducer of apoptosis(TWEAK)/fibroblast growth factor-inducible 14(Fn14)pathway in mice with pulmonary fibrosis,and to investigate its effects and mechanism on pulmonary fibrosis in mice.Methods A total of fifty C57B/L mice were randomly divided into blank group,model group,positive control group{1,25-dihydroxyvitamin D_(3)[1,25(OH)_(2)D_(3)]group},Danshen Tongluo Jiedu decoction group and Danshen Tongluo Jiedu decoction+TWEAK/Fn14 inhibitor(PDL192)group.The mice in the model group,1,25(OH)_(2)D_(3) group,Danshen Tongluo Jiedu decoction group and Danshen Tongluo Jiedu decoction+PDL192 group were injected intratracheally with bleomycin to establish pulmonary fibrosis model.After successful modeling,the mice in the control group and model group were gavaged with saline 10 mL·kg^(-1) daily;the mice in the 1,25(OH)_(2)D_(3) group were injected with 5μg·kg^(-1) of 1,25(OH)_(2)D_(3) intraperitoneally daily;the mice in the Danshen Tongluo Jiedu decoction group were gavaged with Danshen Tongluo Jiedu decoction 0.039 mL·g^(-1) daily(equivalent to 15.65 g·kg^(-1) of raw drug based on adult body mass of 60 kg);the mice in the Danshen Tongluo Jiedu decoction+PDL192 group were gavaged with Danshen Tongluo Jiedu decoction 0.039 mL·g^(-1) and injected with PDL1923 mg·kg^(-1) intraperitoneally;the mice in each group were administered once a day for 28 d.The body mass of mice in each group was measured at 12 h after the last dose,then the mice were anesthetized and fixed by intraperitoneal injection of sodium pentobarbital,bronchoalveolar lavage fluid(BALF)was collected,lung tissue was taken from the open chest,lung mass was measured,and the lung coefficients of mice were calculated.The levels of interleukin 1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin 4(IL-4)in BALF of mice in the five groups were measured by enzyme marker.The histopathological changes of the lungs of mice in the five groups were observed b

关 键 词：肺纤维化 丹参通络解毒汤 博莱霉素 肿瘤坏死因子样弱凋亡诱导因子 成纤维细胞生长因子诱导14 

分 类 号：R285.5[医药卫生—中药学] R563[医药卫生—中医学]