CAJ | 학술논문

目的评价糖皮质激素受体(GR)在大鼠内毒素性急性肺损伤中的作用及可能机制.方法成年雄性SD大鼠60只,体重180 ～ 230 g,采用随机数字表法,将其随机分为4组:对照组(C组,n=6)、RU486组(GR特异性拮抗剂组,R组,n=6)、急性肺损伤组(ALI组,n=24)、RU486+ ALI组(RA组,n=24).ALI组尾静脉注射内毒素(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,R组皮下注射GR拮抗剂RU486 20 mg/kg,RA组注射RU486 20 mg/kg 90 min后注射LPS.ALI组及RA组分别于注射LPS后1、3和6 h(T1～3)时,各组随机取8只大鼠,C组与R组于注射生理盐水、RU486 1 h后处死取肺,检测p-p38MAPK、丝裂原活化蛋白激酶磷酸酶-1(MKP-1)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；计算细胞凋亡指数；观察肺组织病理学结果.另取32只大鼠,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)、RU486+ ALI组(RA1组),处理方法同上.观察48 h内大鼠生存情况.结果与C组相比,ALI组、RA组BALF蛋白浓度和TNF-α浓度、细胞凋亡指数升高(P＜0.05)、病理学损伤加重；T1～3时p-p38MAPK表达上调,ALI组T2,3时MKP-1表达下调,RA组T1-3时MKP-1表达下调(P＜0.05)；与ALI组相比,RA组BALF蛋白浓度和TNF-α浓度、细胞凋亡指数增加,T1～3时p-p38MAPK表达上调(P＜0.05),T2.3时MKP-1表达差异无统计学意义(P＞0.05),RA1组大鼠生存率低于ALI1组(P＜0.05).结论 GR参与大鼠内毒素急性肺损伤的发生发展,其机制与抑制p38MAPK信号转导通路,降低肺组织细胞凋亡有关.
목적 평개당피질격소수체(GR)재대서내독소성급성폐손상중적작용급가능궤제.방법 성년웅성SD대서60지,체중180 ～ 230 g,채용수궤수자표법,장기수궤분위4조:대조조(C조,n=6)、RU486조(GR특이성길항제조,R조,n=6)、급성폐손상조(ALI조,n=24)、RU486+ ALI조(RA조,n=24).ALI조미정맥주사내독소(LPS)5 mg/kg제비대서급성폐손상모형,C조급여등용량생리염수,R조피하주사GR길항제RU486 20 mg/kg,RA조주사RU486 20 mg/kg 90 min후주사LPS.ALI조급RA조분별우주사LPS후1、3화6 h(T1～3)시,각조수궤취8지대서,C조여R조우주사생리염수、RU486 1 h후처사취폐,검측p-p38MAPK、사렬원활화단백격매린산매-1(MKP-1)적표체.T3시회수지기관폐포관세액(BALF),측정단백화TNF-α적농도；계산세포조망지수；관찰폐조직병이학결과.령취32지대서,체중180 ～ 230 g,채용수궤수자표법,장기수궤분위2조(n=16):급성폐손상조(ALI1조)、RU486+ ALI조(RA1조),처리방법동상.관찰48 h내대서생존정황.결과 여C조상비,ALI조、RA조BALF단백농도화TNF-α농도、세포조망지수승고(P＜0.05)、병이학손상가중；T1～3시p-p38MAPK표체상조,ALI조T2,3시MKP-1표체하조,RA조T1-3시MKP-1표체하조(P＜0.05)；여ALI조상비,RA조BALF단백농도화TNF-α농도、세포조망지수증가,T1～3시p-p38MAPK표체상조(P＜0.05),T2.3시MKP-1표체차이무통계학의의(P＞0.05),RA1조대서생존솔저우ALI1조(P＜0.05).결론 GR삼여대서내독소급성폐손상적발생발전,기궤제여억제p38MAPK신호전도통로,강저폐조직세포조망유관.
Objective To evaluate the role of glucocorticoid receptor (GR) in acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.Methods Sixty male Sprague-Dawley rats,weighing 180-230 g,were randomly divided into 4 groups:control group (group C,n =6) ; GR specific inhibitor RU486 group (group R,n =6) ; ALI group (n =24) ; RU486 + ALI group (group RA,n =24).ALI was induced by injection of LPS 5 mg/kg via the tail vein in groups ALI and RA,while the equal volume of normal saline was given in group C and RU486 20 mg/kg was injected subcutaneously in group R.RU486 20 mg/kg was injected subcutaneously 90 min before LPS administration in group RA.Eight rats were chosen at 1,3,and 6 h after LPS administration (T11-3) in groups ALI and RA and at 1 h after normal saline or RU486 administration in groups C and R and sacrificed.The lungs were removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase (pp38MAPK) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in lung tissues.The concentrations of albumin and TNF-α in bronchoalveolar lavage fluids (BALF) were detected,histopathological changes in lung tissues were observed and apoptosis index (AI) was calculated at T3.Another 32 Sprague-Dawley rats,weighing 180-230 g,were randomly divided into 2 groups (n =16 each):group ALI1 and group RA1.The rats were treated as the method mentioned above and observed for the 48 h survival rate.Results Compared with group C,the concentrations of protein and TNF-α in BALF and AI were significantly increased,the histopathological damage was aggravated,and p-p38MAKP expression was up-regulated at T1-3 in groups ALI and RA,and MKP-1 expression was downregulated at T2,3 in group ALI and at Ti-3 in group RA (P ＜ 0.05).Compared with group ALI,the concentrations of protein and TNF-α in BALF and AI were significantly increased,p-p38MAKP expression was up-regulated at T1-3 (P ＜ 0.05),and no significant change was found in MKP-1 expression at T2,3 in group RA (P ＞ 0.05).The 48 h survival rate was significantly lower in group RA1 than in group ALI1 (P ＜ 0.05).Conclusion Glucocorticoid receptors are involved in the development of LPS-induced ALI,and the mechanism may be related to the inhibition of p38MAPK signal transduction pathways and decrease in cell apoptosis in rat lung tissues.