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1、摘要摘要目的:觀察L-NAME對嚴重燙傷早期大鼠血腦屏障通透性和MMP.9表達的影響,探討MMP.9與嚴重燙傷引起的血腦屏障損傷之間的關(guān)系。方法:建立30%TBSAIII度嚴重燙傷大鼠模型。健康成年SpragueDawlay大鼠,隨機分為四組:正常對照組(A);假燙傷組(B);燙傷組(C);燙傷+L.NAME治療組(D)。C、D組又設(shè)嚴重燙傷后3、6、12、24、48h5個時相點,用透射電鏡觀察血腦屏障超微結(jié)構(gòu)變化;紫外分光光度計檢測腦組織伊文氏藍含量;干濕重法測腦含水量;免疫組化染色觀察腦MMP.9表達。結(jié)果:嚴重燙傷后大鼠腦組織伊文氏藍含量、腦含水量明顯增高,MMP.9表達升高,差別具有顯
2、著性(P<0.01)。電鏡顯示:燙傷后大腦皮質(zhì)的神經(jīng)細胞線粒體腫脹或溶解,突觸小泡減少,突觸間隙增寬。腦毛細血管周圍出現(xiàn)空泡化,內(nèi)皮腫脹,基底膜厚薄不均。用一氧化氮合酶抑制劑L.NAME治療后,腦組織伊文氏藍含量及腦含水量與假燙傷組比較明顯下降,經(jīng)L.NAME治療后MMP.9表達恢復(fù)至正常水平,腦毛細血管、神經(jīng)細胞、突觸及基底膜等超微結(jié)構(gòu)基本恢復(fù)正常。結(jié)論:嚴重燙傷后大鼠血腦屏障通透性增高與腦內(nèi)MMP.9表達升高有關(guān),提示MMP·9是嚴重燙傷后血腦屏障損傷的關(guān)鍵因素。早期應(yīng)用L-NAME能明顯減輕燙傷對BBB的損傷,可能與L.NAME抑制MMP.9表達有關(guān)。關(guān)鍵詞:燙傷:血腦屏障;L.硝基.精
3、氨酸甲酯;基質(zhì)金屬蛋白酶.9UAbstractABSTRACTobjective:ToobservetheeffectsofL-NAMEonblood—brainbarrierpermeabilityandMMP-9expressioninratsattheearlystagesofseverescaldinordertoaddresswhetherBBBdysfunctioncausedbyscaldisassociated、析tllMMP-9overexpression.Methods:Toestablishmodelofathird-degreebumaffecting30%ofthet
4、otalbodysurfacearea.HealthyadultSpragueDawlayratsweredividedintofourgroupsasfollowing:normalcontrol(A),sham-scaldedgroup(B),scaldgroup(C),scald+L-NAMEgroup(D),thelatertwogroupswerequantifiedat3,6,12,24,and48hpostthermalinjury.1nleultrastructuralchangeofblood-brainbarrierWasobservedbytransmissionelec
5、tronmicroscope;BrainEvansbluecontentWasexaminedwitlltheultravioletspectrophotometer;BrainwatercontentWasdetectedbycaculatingdry/wetweight;ThechangeofbrainMMP一9expressionafterseverescaldwasdeterminedbyimmunohistochemicalmethod.Results:BrainwatercontentandEvansbluecontentweresignificantlyincreasedafte
6、rburn.ExpressionofbrainMMP-9inratsafterseverescaldWashigherthanthatofshamcontrolgroup’S,andthedifferenceWasconsideredsignificantly(P<0.01).Undertransmissionelectronmicroscope,mitochondrionofsomeneuronsofthecerebralcortexwereswollenordissolved,thenumberofsynapesvesciledecreasedandsynapticcleftbroaden
7、ed.Therewerevacuolated,swollenendothelium,abnormityofcapillarybasementmembranesofBBB.BrainwatercontentandEvansbluecontentdecreasedinseriousscaldedratsaftertheyweretreatedwitllL-NAME.111echangesofultra