吡非尼酮抗百草枯中毒小鼠肺纤维化的研究  

The study of effects of pirfenidone on the pulmonary fibrosis induced by paraquat in mice

作　　者：李军伟[1] 沈秀微[1] 孙未 肖敏[2] 仝淑花[1] 虞希冲[3] 卢中秋[4] 胡国新[3] 

机构地区：[1]温州医学院药学院分子药理与毒理研究所,325035 [2]温州医学院药学院实验动物中心,325035 [3]温州医学院药学院药理教研室,325035 [4]温州医学院药学院附属第一医院急诊中心,325035

出　　处：《中华劳动卫生职业病杂志》2011年第2期87-93,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：浙江省医学扶植重点建设学科计划项目（07-F04）;浙江省教育厅科研重点项目（Z200803373）;浙江省自然科学基金项目（Y-2080977）

摘　　要：目的探讨吡非尼酮（PF）对百草枯（PQ）中毒小鼠肺纤维化的治疗作用，为临床治疗提供理论依据。方法雄性ICR小鼠90只，随机分为正常对照组、PQ组、地塞米松组、25、50和100mg／kgPF组，每组15只。正常对照组小鼠一次性空腹灌胃给予生理盐水，2h后给予质量分数为1％羧甲基纤维素（CMC）灌胃，再每天定时空腹灌胃同等量CMC；PQ组、地塞米松组及各PF剂量组小鼠给予PQ100mg／kg一次性灌胃染毒，灌胃后2h，再每天定时PQ组给予0．02ml／lOgCMC灌肠，PF组给予PF（25、50、100mg／kg）和地塞米松（0．02ml／10g）灌胃，每天1次，共49d。计算肺系数，HE染色，光学显微镜下观察肺组织病理改变；测定肺组织羟脯氨酸（HYP）含量，转化生长因子（TGF—β）的mRNA表达水平、蛋白表达水平，支气管肺泡灌洗液（BALF）中的TGF—β，蛋白含量。结果PQ组3d生存率为53．33％，25、50、100mg／kgPF组3d生存率分别为46．67％、73．33％、86．67％，地塞米松组3d生存率为80％，地塞米松组、50、100mg／kgPF组3d生存率明显高于PQ组和25mg]kgPF组，差异有统计学意义（P〈0．05）。25、50及100mg／kgPF组小鼠肺系数均明显低于PQ组，差异有统计学意义（P〈0．05）。地塞米松组肺组织中HYP含量为（50．95±11．65）mg／g，25、50、100mg／kgPF组HYP含量分别为（44．52±9．48）、（43．27±6．01）、（40．82±5．90）mg／g，较PQ组[（74．27±3．68）mg／g]明显下降，差异均有统计学意义（P〈0．01）。地塞米松组BALF中TGF-β1蛋白含量为（22．03±7．27）mg／ml，25、50、100mg／kgPF组TGF-β1蛋白含量分别为（55．33±17．50）、（27．75±5．84）、（21．31±6．82）mg／ml，与PQ组[（52．52±15．51）mg／m1]相比，明显降低，差异有统计学意义（P〈0．01）；100mg／kgPF组肺组织TGF—β1 mRNA表达水平与PQ组相比，明显下降，差异有统计学意Objective To study the curative effects of pirfenidone （PF）on pulmonary fibrosis induced by paraquat （PQ） in mice and to provide the theoretical basis for clinical treatment. Methods Ninety adult healthy male ICR mice were randomly divided into six groups： control group, PQ group , 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/log dexamethasone and 25,50,100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each .day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline （HYP） level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β1 in lung tissue for each mouse were determined, and the protein level of TGF-β1 in the bronchus-alveolus lavage fluid （BALF） of each mouse was detected. Results The survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group （P〈0.05）. The lung coefficients of 3 PF groups were significantly lower than that of the PQ group （P〈0.05）. The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95± 11.65, 44.52±9.48, 43.27±6.01 and 40.82±5.90 mg/g respectively, which were significantly lower than that （74.27±3.68） of PQ g

关 键 词：百草枯 肺纤维化 吡非尼酮 羟脯氨酸 转化生长因子Β 

分 类 号：R285.5[医药卫生—中药学]