CAJ | 학술논문

目的评价地塞米松对内毒素性急性肺损伤大鼠肺组织丝裂原活化蛋白激酶磷酸酶-1(MKP-1)表达的影响.方法成年雄性SD大鼠54只,体重180～ 230 g,采用随机数字表法,将其随机分为3组:对照组(C组,n=6)、急性肺损伤组(ALI组,n=24)和地塞米松组(D组,n=24).ALI组和D组尾静脉注射LPS 5 mg/kg制备大鼠急性肺损伤模型,C组给予等容量生理盐水,D组于注射LPS前30 min时腹腔注射地塞米松6 mg/kg.C组于注射生理盐水后1 h(T1)时,ALl组和D组分别于注射LPS后1、3和6 h(T1-3)时,随机处死8只大鼠,取肺组织,检测MKP-1和磷酸化p38丝裂原活化蛋白激酶MAKP(p-p38MAPK)的表达.T3时回收支气管肺泡灌洗液(BALF),测定蛋白和TNF-α的浓度；观察肺组织病理学结果.另取32只SD大鼠,体重180～ 230 g,采用随机数字表法,将其随机分为2组(n=16):急性肺损伤组(ALI1组)和地塞米松组(D1组),处理方法同上.观察48 h内大鼠生存情况.结果与C组比较,ALI组BALF中蛋白和TNF-α的浓度升高,T1-3时p-p38MAKP表达上调,T2.3时MKP-1表达下调,D组BALF中TNF-α浓度升高,T1-3时p-p38MAKP和MKP-1表达上调(P＜0.05)；与ALI组比较,D组BALF中蛋白和TNF-α的浓度下降,T1-3时p-p38MAKP表达下调,MKP-1表达上调(P＜0.05),病理学损伤减轻.D1组大鼠生存率高于ALI1组(P＜0.05).结论地塞米松减轻大鼠内毒素性急性肺损伤的机制与上调肺组织MKP-1的表达,抑制p38MAPK的磷酸化,降低炎性反应有关.
목적 평개지새미송대내독소성급성폐손상대서폐조직사렬원활화단백격매린산매-1(MKP-1)표체적영향.방법 성년웅성SD대서54지,체중180～ 230 g,채용수궤수자표법,장기수궤분위3조:대조조(C조,n=6)、급성폐손상조(ALI조,n=24)화지새미송조(D조,n=24).ALI조화D조미정맥주사LPS 5 mg/kg제비대서급성폐손상모형,C조급여등용량생리염수,D조우주사LPS전30 min시복강주사지새미송6 mg/kg.C조우주사생리염수후1 h(T1)시,ALl조화D조분별우주사LPS후1、3화6 h(T1-3)시,수궤처사8지대서,취폐조직,검측MKP-1화린산화p38사렬원활화단백격매MAKP(p-p38MAPK)적표체.T3시회수지기관폐포관세액(BALF),측정단백화TNF-α적농도；관찰폐조직병이학결과.령취32지SD대서,체중180～ 230 g,채용수궤수자표법,장기수궤분위2조(n=16):급성폐손상조(ALI1조)화지새미송조(D1조),처리방법동상.관찰48 h내대서생존정황.결과 여C조비교,ALI조BALF중단백화TNF-α적농도승고,T1-3시p-p38MAKP표체상조,T2.3시MKP-1표체하조,D조BALF중TNF-α농도승고,T1-3시p-p38MAKP화MKP-1표체상조(P＜0.05)；여ALI조비교,D조BALF중단백화TNF-α적농도하강,T1-3시p-p38MAKP표체하조,MKP-1표체상조(P＜0.05),병이학손상감경.D1조대서생존솔고우ALI1조(P＜0.05).결론 지새미송감경대서내독소성급성폐손상적궤제여상조폐조직MKP-1적표체,억제p38MAPK적린산화,강저염성반응유관.
Objective To investigate the effect of dexamethasone on mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in lung tissues in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Fifty-four male SD rats weighing 180-230 g were randomly divided into 3 groups:control group (group C,n =6) ;ALI group ( n =24) and dexamethasone group (group D,n =24).LPS 5 mg/kg was injected via tail vein in groups ALI and D,while the equal volume of normal saline was given in group C.Dexamethasone 6 mg/kg was injected intraperitoneally at 30 min before LPS administration in group D.Eight rats in each group were sacrificed at 1 h after normal saline administration (T1) in group C and at 1,3,and 6 h after LPS administration (T1-3 ) in groups ALI and D.The lung tissues were then removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) and MKP-1.The concentrations of albumin and TNF-α in bronchoalveolar lavage fluid (BALF) were detected and histopathological changes were observed at T3 ·Another 32 SD rats weighing 180-230 g were randomly divided into 2 groups ( n =16 each):group ALI1 and group D1.The rats were treated as the method mentioned above and the 48 h survival condition was observed.Results Compared with group C, the concentrations of protein and TNF-α in BALF were significantly increased,p-p38MAKP expression was up-regulated at T1.3,and MKP-1 expression was down-regulated at T2,3 in group ALI,and TNF-α concentration in BALF was significantly increased and the expression of p-p38MAKP and MKP-1 was up-regulated at T1-3 in group D ( P ＜ 0.05).Compared with group ALI,the concentrations of protein and TNF-α in BALF were significantly decreased,p-p38MAKP expression was down-regulated and MKP-1 expression was up-reg-ulated at T1-3 ( P ＜ 0.05 ),and the pathological damage was attenuated in group D.The 48 h survival rate was significantly higher in group D1 than in group ALI1 ( P ＜ 0.05).Conclusion The mechanism by which dexamethasone attenuates the ALI induced by LPS may be related to up-regulation of MKP-1,inhibition of phosphorylation of p38MAPK and decrease in inflammatory response.