双氢青蒿素对染尘大鼠肺纤维化治疗作用的研究  

Therapeutic effect of dihydroartemisinin on pulmonary fibrosis in rats with dust

作　　者：郑熠娇 李侠[2] 孙琳 郭敬文[1,2] Zheng Yijiao;Li Xia;Sun Lin;Guo Jingwen(School of Medicine and Life Science,Universicy of Jinan-Shandong Academy of Medicine Sciences,Jinan 250062,China;Shandong Academy of Medical Sciences Shandong Academy of Occupational Health and Occupational Medicine,Jinan 250062,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,250062 [2]山东省医学科学院、山东省职业卫生与职业病防治研究院,济南250062

出　　处：《中华劳动卫生职业病杂志》2019年第2期96-103,共8页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的观察双氢青蒿素(Dihydroartemisinin,DHA)对染尘大鼠肺纤维化的治疗作用,比较DHA和汉方己甲素两种药物的治疗效果。方法将60只雄性SD大鼠随机分为对照组、模型组、治疗1组和治疗2组,每组15只,模型组和治疗组采用一次性非暴露式二氧化硅气管滴注法染尘,染尘后第2天开始给药,治疗1组给予DHA 75mg/kg灌胃,治疗2组给予汉方己甲素22 mg/kg,模型组和对照组按每100g/kg体重灌胃1ml生理盐水,每周给药6 d,连续给药4周。在染尘后的第7、14、28天每组处死大鼠5只,取大鼠肺组织,检测大鼠肺系数,酶联免疫吸附(ELISA)法检测大鼠肺组织中转化生长因子-1(TGF-β1)、细胞信号转导分子(Smad 2/3)、Ⅰ型胶原蛋白(Col-Ⅰ)表达水平,大鼠肺组织病理学变化,免疫组化观察大鼠肺组织TGF-β1和Col-I蛋白表达。用SPSS 19.0进行统计分析,多组组间均数比较采用完全随机设计单因素方差分析(ANOVA)。结果与模型组比较,治疗组大鼠肺组织中TGF-β1、Smad 2/3、Col-I表达降低,差异均有统计学意义(P<0.05),治疗1组和治疗2组之间差异无统计学意义(P>0.05)。免疫组化结果显示,模型组大鼠肺间质内TGF-β1和Col-I蛋白强阳性表达,治疗组大鼠肺间质内TGF-β1和Col-I蛋白表达较模型组弱。结论DHA可以下调大鼠肺组织中炎性细胞因子水平,可通过干预TGF-β1/Smad 2/3信号通路抑制肺纤维化,但DHA和汉防己甲素两者间的治疗效果在短时间内无明显差异。Objective To observe the therapeutic effect of dihydroartemisinin on pulmonary fibrosis in rats exposed to dust,and compare the therapeutic effects of dihydroartemisinin and tetrandrine.Methods Sixty male Sprague-Dawley rats were randomly divided into control group,model group,treatment group 1 and treatment group 2,with 15 rats in each group.The model group and the treatment group were stained with disposable non-exposure silica tracheal instillation method.The drug was administered on the second day after the dust was applied.The treatment group was given with dihydroartemisinin 75 mg/kg,the treatment group was given tetrahexine 22 mg/kg,model group and control group were intragastrically administered with 1 ml of normal saline per 100 g of body mass.The drug was administered for 6 days per week for 28 days.Rats were sacrificed on the 7th,14th and 28th day after dusting,and the lung tissues of rats were taken,detection of rat lung coefficient,ELISA was used to detect transforming growth factor-1(TGF-1)and Smad 2/3 in rat lung tissues,type I collagen(Col-I)expression level,pathological changes of rat lung tissue,immunohistochemical observation of rat lung tissue TGF-1 and Col-I protein expression.Statistial analysis was proformed with SPSS 19.0.The mean cornparis between graups wad perfomed using a completely randonized one-way(ANOVA).Results The expressions of TGF-1,Smad 2/3 and Col-I in the lung tissue of the treatment group were significantly lower than those in the model group(P<0.05),but the difference between the treatment group 1 and the treatment group 2 Not statistically significant(P>0.05).The results of immunohistochemistry showed that the TGF-1 and Col-I proteins in the interstitial of the model group showed strong positive expression.The expression of TGF-1 and Col-I protein in the lung interstitial of the treated group was weaker than that of the model group.Conclusion Dihydroartemisinin can down-regulate the level of inflammatory cytokines in rat lung tissue.It is possible to inhibit pulmonary fib

关 键 词：双氢青蒿素 汉方己甲素 大鼠 肺纤维化 

分 类 号：R135.2[医药卫生—劳动卫生]