基于NF-κB信号转导通路探讨加味补阳还五汤对肺纤维化小鼠的治疗作用  

Study on the therapeutic effect of Modified Buyanghuanwu Decoction on pulmonary fibrosis in mice based on NF-κB signal transduction pathway

作　　者：杨善军[1] 祝鹏宇[2] 王玥[1] 曲齐生[1] 曲阳 邢露茗 封笑 肖洋 樊蓉[3] YANG Shanjun;ZHU Pengyu;WANG Yue;QU Qisheng;QU Yang;XING Luming;Feng Xiao;XIAO Yang;FAN Rong(Department of Pulmonary Disease,Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Haerbin 50001,China;Department of Acupuncture Second Ward,Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Haerbin 50001,China;Endocrine Geriatric Disease,Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Haerbin 50001,China)

机构地区：[1]黑龙江中医药大学附属第二医院肺病科,哈尔滨150001 [2]黑龙江中医药大学附属第二医院针灸二病房,哈尔滨150001 [3]黑龙江中医药大学附属第二医院内分泌老年病科,哈尔滨150001

出　　处：《新疆医科大学学报》2020年第3期329-334,共6页Journal of Xinjiang Medical University

基　　金：哈尔滨市科技创新人才研究专项资金/青年后备人才公益类项目(2017RAQXJ189)。

摘　　要：目的探讨加味补阳还五汤对肺纤维化小鼠的治疗作用及加味补阳还五汤各剂量组在小鼠肺组织中NF-κB p65 mRNA和蛋白表达。方法BALB/cJ小鼠120只随机分成6组:对照组、模型组、强的松组(40.0 mg/kg)、加味补阳还五汤低、中、高剂量组。模型组、强的松组、加味补阳还五汤各剂量组小鼠使用博莱霉素构建肺纤维化模型,建模成功后,强的松组及加味补阳还五汤各剂量组给予醋酸强的松混悬液(0.32 mg/mL)以及各剂量的加味补阳还五汤(10、20、40 mg/mL)灌胃,连续14 d。试验结束后,处死小鼠,获取肺组织进行小鼠肺泡炎级别、肺纤维化级别评分,逆转录-聚合酶链反应(RT-PCR)法及免疫组织化学法测定肺组织核因子-κB(NF-κB)p65 mRNA和蛋白水平,Elisa法检测肺组织HYP、IL-4、TNF-α蛋白水平。结果与对照组比较,模型组肺泡炎级别评分、肺纤维化级别评分、肺组织NF-κB p65 mRNA和蛋白、HYP、IL-4、TNF-α蛋白表达明显升高(P<0.05);与模型组比较,强的松组、加味补阳还五汤各剂量组肺泡炎级别评分、肺纤维化级别评分、肺组织NF-κB p65 mRNA和蛋白、HYP、IL-4、TNF-α蛋白表达降低(P<0.05),且随着加味补阳还五汤给药剂量的增加,肺泡炎级别评分、肺纤维化级别评分、肺组织NF-κB p65 mRNA和蛋白、HYP、IL-4、TNF-α蛋白表达逐渐降低(P<0.05);与强的松组相比,加味补阳还五汤低、中剂量组肺泡炎级别评分、肺纤维化级别评分、肺组织NF-κB p65 mRNA和蛋白、HYP、IL-4、TNF-α蛋白表达升高(P<0.05);高剂量组肺泡炎级别评分、肺纤维化级别评分、肺组织NF-κB p65 mRNA和蛋白、HYP、IL-4、TNF-α蛋白表达无明显变化(P>0.05)。结论加味补阳还五汤可以抑制博莱霉素诱导小鼠肺纤维化,其机制与加味补阳还五汤抑制NF-κB p65活化,继而抑制炎症因子及纤维因子的表达有关。Objective To investigate the therapeutic effect of Modified Buyanghuanwu Decoction in treating pulmonary fibrosis murine model and on the expression of NF-t of ilongjiang University of Traditional Chin.Methods120 BALB/cJ mice were randomly divided into 6 groups:control group,model group,prednisone group(40.0 mg/kg),low,medium and high dose groups of Modified Buyanghuanwu Decoction.The mice in the model group,prednisone group and Modified Buyanghuanwu Decoction were used to establish pulmonary fibrosis model.After successful modeling,prednisone group and Modified Buyanghuanwu Decoction were given prednisone acetate suspension(0.32 mg/mL)and Modified Buyanghuanwu Decoction(10,20,40 mg/mL)by gavage for 14 days.At the end of the experiment,mice were executed,and lung tissues were obtained for the grade of alveolitis and pulmonary fibrosis.The levels of NF-κB p65 mRNA and protein in lung tissues were determined by RT-PCR and immunohistochemistry.The levels of HYP,IL-4 and TNF-αprotein in lung tissues were detected by ELISA method.ResultsCompared with the control group,the alveolar inflammation grade score,pulmonary fibrosis grade score,and NF-κB p65 mRNA and protein,HYP,IL-4,and TNF-αprotein expression in the model group were significantly increased(P<0.05).Compared with the control,the prednisone group and Jiawei Buyang Huanwu Decoction group had lower alveolar inflammation grade score,pulmonary fibrosis grade score,lung tissue NF-κB p65 mRNA and protein,HYP,IL-4,TNF-αprotein expression(P<0.05),and with the increase of the dosage of Buyang Huanwu Decoction,the alveolitis grade score,pulmonary fibrosis grade score,NF-κB p65 mRNA and protein,HYP,IL-4,TNF-αAlpha protein expression gradually decreased(P<0.05);compared with the prednisone group,Jiawei Buyang Huanwu Decoction was low,medium-dose group alveolitis grade score,pulmonary fibrosis grade score,NF-κB p65 mRNA and protein in lung tissue,HYP,IL-4,TNF-αprotein expression increased(P<0.05);high-dose group alveolitis grade score,pulmonary fibrosis grade scor

关 键 词：加味补阳还五汤 肺纤维化 NF-ΚB信号转导通路 作用机制 

分 类 号：R256.15[医药卫生—中医内科学] R28[医药卫生—中医学]