The Curative Effect Of Dihydroartemisinin On Paraquat-Induced Pulmonary Fibrosis In A Mice Model

Objective To explore the overall level, pathological changes of lungtissure and the value of transforming growth factor-β1（TGF-β1） expressions in amice model of pulmonary fibrosis induced by paraquat （PQ）,and evaluate thecurative effects of dihydroartemisin（DHA）in this model.Methods220mice were randomizedly assigned into4groups: the controlgroup（N group，n=55）、model of pulmonary fibrosis group（PQ group,n=55, theactual survivals were24）、treatment groups: the prednisone acetate group（PAgroup,n=55,the actual survivals were29）、DHA group（n=55,the actual survivalswere35）. PQ (100mg.kg^-1) was administered to the animals in PQ group, PAgroup and DHA group only once by intragastric administration.2h later, PAgroup was cured by intragastric administration of6mg.kg^-1PA, DHA groupwas cured by intragastric administration of20mg.kg^-1DHA, the control groupand PQ group were givend the carboxymethylcellulose sodium（CMC）once aday.The mice were killed on day3、7、14、21．The indexes of test included：general conditions， differences in survivals, lung coefficient,TGF-β1wasexamined in the lung tissues by enzyme-linked immuno sorbent assay （ELISA）,pulmonary inflammation and fibrosis of mice in different groupswere observed by pathological methods. Then process statistical analysis.Results The toxic response showed serious in each group.The survivalrate on21th day in PQ group was minimum than the control group and DHAgroup（P＜0.05）.The lung tissues showed great edematous and lung congestionin PQ group,and the lung coefficient obviously rose which had statisticalsignificance compared with the control groups（P<0.001） and DHAgroup（P<0.05）. DHA group got the lighter general conditions,TGF-β1levels ofDHA group on day14、21were lower as compared with PQ group （P＜0.01）.While TGF-β1expressions in PA group didn’t show statistical significancecompared with the PQ groups,as compared with the DHA group （P＜0.01）.The pathological changes of PQ group became severer than the control group astime went by.On14th day,PQ group showed pulmonary fibrosis inpathomorphology with an increasing of TGF-β1and peaked on the21th day,which had statistical significance compared with the control group（P<0.01）.Pathological changes in PA group and DHA group meant the same variation,butthe PA group hadn’t statistical significance compared with PQ group,while DHAgroup showed milder inflammation and pulmonary fibrosis in lung tissues thanPQ group （P＜0.05）.Conclusions①An pulmonary fibrosis model of mice can be successestablished by intragastric administration of100mg.kg^-1paraquat.②TGF-β₁might play an important role in pulmonary fibrosis induced byparaquat.③DHA could reduce the pulmonary fibrosis induced by PQ in mice in away of reducing the lung wet weight,relieving inflammation and pulmonaryfibrosis in lung tissues and reducing TGF-β1expressions. ④Corticosteroids show ineffective in pulmonary fibrosis induced byparaquat in a mice model.