Effects Of Heroin On Antioxidant Enzymes Activity, Histological Structure And Expression Of Inter Related Polypeptides In The Lungs Of The Filial Mice And Mother Mice

ObjectiveIn order to study the effects of heroin on weight,behaviour changes and enzymaticactivityofsuperoxidedismutase(SOD)andcatalase(CAT),andmaleicdialdehyde(MDA)content and histological structure and positive expression of KGF,c-Fos and Bax in thelungs of the developing filial mice and mother mice by separate injecting into pregnantmicewithdifferentconcentrationsofheroin,toprovidebasicdatafortheresearchonlungdevelopmentinanimals.Methods48 mother mice at the eighth day of pregnancy began to be separately injected withdifferent concentrations (1.0 g/L,1.5 g/L and 2.0 g/L) of heroin (0.2 ml) in theexperimental groups and the same amount of saline in the control group in the morningand afternoon until the birth of filial mice. Changes of weight and behaviour wereobserved and the enzymatic activity of SOD,CAT and MDA content were respectivelyanalyzed by colorimetry in the lungs of filial mice and mother mice at embryo 15 andpostnatal ages of 1 d, 7 d, 15 d,the lung structure were observed by microscope andexpression of KGF,c-Fos and Bax were measured by immunohistochemistry combinedwith stereological methods in the lungs of filial mice and mother mice at the differentdevelopmentalstages.Results1. Heroin influenced behaviour and weight of filial mice and mother mice andembryonic development of filial mice.Inthe experimental groups mother mice appearedsymptomssuchasexcitedrunning,jumping,diarrheaandfilialmiceappearedsymptomssuch as number decrease at the breast and screaming and writhing number increase,alsothe weight of filial mice and mother mice of the experimental groups was lower than thecontrol groups at the different developmental stages.2.0 g/Lheroin group appeared deadandabnormalfetalmice.2. Heroin affected theantioxidant enzymes activity in the lungs of of filial mice andmothermice,therewasasignificantinhibitionfortheSOD,CATactivity(P<0.05)withheroin,and the inhibitive effects were stronger with the concentration of heroin increasing,but the MDAcontent significantly increased (P < 0.05) and was higher withtheincreasedconcentrationofheroin.3. Heroin affected the lunghistological structure of filial mice and mother mice,thediameterofalveolousandthicknessofinteralveolarseptumoffilialmiceandmothermicesignificantlyincreased(P<0.05)withinjection1.5g/Land2.0g/Lherointhanthat ofthecontrol at the different developmental stages,while the diameter of alveolous andthickness of interalveolar septum didn't significantly change with injection 1.0 g/Lheroin(P>0.05).4. Heroin affected the expression of inter related polypeptides in the lungs of the filialmiceandmothermice,thepositiveexpressionofKGF,c-FosandBaxinthelungsoffilialmiceandmothermicesignificantlyincreased(P<0.01orP<0.05)withinjection1.5g/Land2.0g/Lherointhanthatofthecontrolatthedifferentdevelopmentalstages,whilethepositive expression of KGF,c-Fos and Bax didn't significantly change with injection 1.0g/Lheroin(P>0.05),andthepositive expressionwerestronger withthe concentrationofheroin increasing.However, during the following development, the positive expressionofKGF,c-FosandBaxdecreasedgraduallyinthelungsoffilialmiceandmothermiceoftheheroingroups.Conclusion1. The influence of heroin had long time-history effect for the behaviour and weightofdevelopingfilialmiceandmothermiceandembryonicdevelopment.2. The activities of SOD,CAT activity were injuryed in the lungs of filial mice andmother mice at the different developmental stages byheroin,and lipid peroxidation leveloflungswereincreasedduringdevelopmentofthefilialmiceandmothermice,thenlungcellsweredamagedbyheroin.3. The lung structure of filial mice and mother mice at the different developmentalstagesweredamagedindifferentdegreesbyheroin,andthedamageweresignificantwiththeconcentrationofheroinincreasing.4. Heroin affected positive expression of KGF,c-Fos and Bax in the lungs of thedevelopingfilialmiceandmothermiceatthedifferentdevelopmentalstages,whichledtothe lung apoptotic cell increase,but the influences were weakening during the followingdevelopmentofthefilialmice. 5. The lungs of filial mice and mother mice at the different developmental stageswere damaged in different degrees by heroin. This damage might be correlated with thelowactivitiesofSOD,CATandhighcontentofMDAandtheincreasesoftheexpressionintensityofKGF,c-FosandBaxinfilialmiceandmothermicelung.