双氢青蒿素对百草枯致小鼠肺纤维化的治疗研究  

THE CURATIVE EFFECT OF DIHYDROARTEMISININ ON PARAQUAT-INDUCED PULMONARY FIBROSIS IN A MICE MODEL

作　　者：陈冰燕[1] 李超乾[1] 覃先连[1] 

机构地区：[1]广西医科大学第一附属医院呼吸内科,南宁530021

出　　处：《广西医科大学学报》2012年第2期175-178,共4页Journal of Guangxi Medical University

基　　金：广西科学基金资助项目(No.0448056)

摘　　要：目的:探讨双氢青蒿素(dihydroartemisin,DHA)对急性百草枯(paraquat,PQ)染毒小鼠的治疗作用。方法:将134只小鼠随机分成3组:正常对照组(n=24)、PQ染毒组(n=55,实际存活24只)和DHA治疗组(n=55,实际存活35只)。PQ组与DHA组:以100mg/kg PQ一次性灌胃;2h后DHA组以20mg/kg DHA灌胃治疗,PQ组与对照组灌胃等量蒸馏水,每日1次。观察给药后第3,7,14,21天小鼠的一般情况,比较生存率差异,计算肺系数,酶联免疫吸附法(ELISA)测定肺组织TGF-β1的表达;HE及Masson染色观察小鼠肺组织病理变化。结果:PQ组21d生存率与对照组和DHA组比较差异有统计学意义(P<0.05)。PQ组肺组织中TGF-β1在第3,7,14,21天分别为(467.77±46.52)ng/L、(434.89±48.94)ng/L、(1 410.70±94.07)ng/L、(2 306.89±33.06)ng/L;DHA组一般情况较PQ组好,TGF-β1表达在第3,7,14,21天时分别为(441.54±23.58)ng/L、(443.22±46.83)ng/L、(750.49±29.96)ng/L、(1 554.95±92.30)ng/L,较PQ组差异显著(P<0.01)。随时间推移,PQ组肺泡炎加重,14d始伴随着TGF-β1的升高,肺组织出现纤维化改变,以第21天时最为明显,与对照组比较差异明显(P<0.01)。DHA组炎性细胞浸润较PQ组少,充血水肿轻,肺纤维化程度较PQ组减轻(P<0.05)。结论:DHA可能通过降低肺组织中TGF-β1表达,发挥对PQ中毒小鼠肺纤维化的治疗作用。Objective：To study the curative effects of dihydroartemisin（DHA） on pulmonary fibrosis induced by paraquat（PQ） in mice.Methods： A total of 134 mice were randomly assigned into control（n=24）,PQ（n=55,survivals 24） and DHA groups（n=55,survivals 35）.PQ（100 mg/kg） was administered to the animals in PQ group and DHA group only once by intragastric administration.Two hours later,DHA group was cured by intragastric administration of 20 mg/kg DHA,control and PQ groups were given the equivalent distilled water once a day.The mice were killed on days 3,7,14 and 21.The indexes of test included general conditions,differences in survivals,and lung coefficient.TGF-β1 in the lung tissues,pulmonary inflammation and fibrosis of mice in different groups were observed by pathological methods（HE staining and Masson staining）.Results： The survival rate on 21th day in PQ group was highest than that in DHA and control groups（P〈0.05）.TGF-β1 levels in lung tissues in PQ group on days 3,7,14 and 21 were（467.77±46.52）,（434.89±48.94）,（1410.70±94.07）,and（2306.89±33.06） ng/L;respectively.DHA group got the lighter general conditions.The ELISA results of TGF-β1 were（441.54±23.58）,（443.22±46.83）,（750.49±29.96）,and（1554.95±92.30） ng/L on days 3,7,14 and 21,as compared with PQ group（P〈0.01）.The pathological changes of PQ group became severer than the control group as time went by.On 14th day,PQ group showed pulmonary fibrosis in pathomorphology with an increasing of TGF-β1 and peaked on the 21th day,as compared with control group（P〈0.01）,and DHA group showed milder lung tissue inflammation and edema than PQ group（P〈0.05）.Conclusion： ① A pulmonary fibrosis model of mice can be successfully established by intragastric administration of 100 mg/kg PQ;② the increased TGF-β1 levels might be the result of pulmonary fibrosis;③DHA could reduce pulmonary fibrosis induced by PQ in mice lungs in a way of reducing TGF-β1.

关 键 词：百草枯 双氢青蒿素 转化生长因子-Β 肺纤维化 小鼠 

分 类 号：R969[医药卫生—药理学]