氧化苦参碱对放射性肺损伤模型小鼠肺纤维化的改善作用及其机制研究  

Effect and mechanism of oxymatrine on pulmonary fibrosis in mice with radiation-induced pulmonary injury

作　　者：王文龙 林胜友[3] 卢宏达[4] 雷章[4] 余涛[4] 吴洪斌[4] 孔庆志[4] WANG Wen-long;LIN Sheng-you;LU Hong-da;LEI Zhang;YU Tao;WU Hong-bin;KONG Qing-zhi(Clinical College of Traditional Chinese Medicine,Hubei University of Traditional Chinese Medicine,Wuhan 430065,Hubei Province,China;Intensive Care Unit,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang Province,China;Department of Oncology,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang Province,China;The Central Hospital of Wuhan,Wuhan 430014,Hubei Province,China)

机构地区：[1]湖北中医药大学中医临床学院,湖北武汉430065 [2]杭州市中医院重症医学科,浙江杭州310007 [3]杭州市中医院肿瘤科,浙江杭州310007 [4]武汉市中心医院,湖北武汉430014

出　　处：《中国临床药理学杂志》2020年第5期503-506,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81372931;81704023);浙江省卫生计生委医药卫生科研面上基金资助项目(2018KY615);浙江省中医药管理局中医药科技计划基金资助项目(2018ZB091);杭州市卫生科技计划基金资助项目(2017A59).

摘　　要：目的研究氧化苦参碱对放射性肺损伤小鼠的作用及其机制。方法用小动物精准放疗辐照研究平台实施单次20 Gy双侧肺野照射建立放射性肺损伤小鼠模型。按照体重将小鼠随机分为4组:正常组、模型组、实验组和对照组,每组8只。正常组和模型组腹腔注射等体积0.9%NaCl,对照组给予地塞米松注射液0.5 mg·kg^-1·d^-1腹腔注射;实验组予以氧化苦参碱40 mg·kg^-1·d^-1,1次/天,连续4周。计算出肺系数,用实时定量-PCR和免疫印迹法分别检测组小鼠肺组织中转化生长因子-β1(TGF-β1)、Smad3(是转化生长因子β信号通路中重要的转换蛋白)、糖原合成酶激酶3β(GSK-3β)和β-连环蛋白(β-catenin)基因及其蛋白的表达水平。结果正常组、模型组、实验组和对照组而的肺系数分别为4.55±0.09,6.65±0.21,5.13±0.15和5.05±0.14;这4组的TGF-β1基因的相对表达量分别为0.64±0.15,1.07±0.11,0.83±0.09和0.82±0.08;这4组的Smad3基因的相对表达量分别为0.57±0.15,1.13±0.26,0.77±0.11和0.75±0.08;这4组的GSK-3β基因的相对表达量分别为0.28±0.06,0.55±0.04,0.45±0.04和0.43±0.12;这4组的β-catenin基因的相对表达量分别为0.17±0.04,0.42±0.06,0.27±0.04和0.26±0.05。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.01);实验组或对照组与模型组比较,差异均有统计学意义(均P<0.01)。蛋白结果的趋势与基因一致。结论氧化苦参碱能够改善放射性肺损伤模型小鼠肺纤维化病变,其作用与抑制TGF-β/Smads及Wnt/β-catenin相关的信号传导通路有关。Objective To investigate the effect and mechanism of oxymatrine on radiation-induced pulmonary injury(RIPI)in mice.Methods RIPI mice model was induced by a single 20 Gy bilateral lung field irradiation with Precision Radiation Research Platform for Small Animals(SARRP).The mice were randomly divided into 4 groups:normal group,model group,control group and experimental group.Mice in normal group and model group were intraperitoneally injected with an equal volume of 0.9% NaCl,mice in control group were intraperitoneally injected with dexamethasone injection 0.5 mg·kg^-1·d^-1,while mice in experimental groups were intraperitoneally injected with oxymatrine at the dose of 40 mg·kg^-1·d^-1,respectively,1 times a day,for consecutive 4 weeks.The pulmonary coefficient was calculated.The expression of transforming growth factor-beta1(TGF-β1),Smad3(as important transforming proteins in transforming growth factor β signaling pathway),glycogen synthase kinase-3β(GSK-3β)and β-cateninin mRNA and protein were detected by real time-PCR and Western blot,respectively.Results The pulmonary coefficient in normal group,model group,experimental group and control group were4.55±0.09,6.65±0.21,5.13±0.15 and 5.05±0.14;respectively;the relative expression levels of TGF-β1 mRNA in the 4 groups were 0.64±0.15,1.07±0.11,0.83±0.09 and 0.82±0.08,respectively;the relative expression levels of Smad3 mRNA in the 4 groups were 0.57±0.15,1.13±0.26,0.77±0.11 and 0.75±0.08,respectively;the relative expression levels of GSK-3β mRNA in the 4 groups were 0.28±0.06,0.55±0.04,0.45±0.04 and0.43±0.12,respectively;the relative expression levels of β-catenin mRNA in the 4 groups were 0.17±0.04,0.42±0.06,0.27±0.04 and 0.26±0.05,respectively.Significant difference of the factors were found between normal group and model group(all P<0.01),and significant difference of the factors were also found between experimental group or control group and model group(all P<0.01).The trend of protein results is consistent with that of mRNA.Con

关 键 词：放射性肺损伤 氧化苦参碱 转化生长因子-Β1 糖原合成酶激酶3Β Β-连环蛋白 

分 类 号：R97[医药卫生—药品]