CHANGES OF PULMONARY GLUCOCORTICOID RECEPTOR AND PHOSPHOLIPASE-A2 IN SHEEP WITH ACUTE LUNG INJURY AFTER HIGH-DOSE ENDOTOXIN INFUSION

被引:41
作者
LIU, LY [1 ]
SUN, B [1 ]
TIAN, Y [1 ]
LU, BZ [1 ]
WANG, J [1 ]
机构
[1] ACAD MIL MED SCI,DEPT PATHOPHYSIOL,BEIJING,PEOPLES R CHINA
来源
AMERICAN REVIEW OF RESPIRATORY DISEASE | 1993年 / 148卷 / 04期
关键词
D O I
10.1164/ajrccm/148.4_Pt_1.878
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
In a sheep model of acute lung injury induced by an Escherichia coli endotoxin (5 mug/kg) with chronic lung lymph fistula (n = 15), we measured the changes in glucocorticoid receptor (GCR) binding capacity in lung tissue by means of radioligand binding assay. The content of cortisol and the activity of phospholipase A2 (PLA2) were also measured. The results showed that the maximal binding capacity (Bmax) of GCR in lung cytoplasma decreased continuously 2 h (113 +/- 3 versus 66 +/- 2 fmol/mg protein, p < 0.01), 4 h (105 +/- 6 versus 52 +/- 3 fmol/mg protein, p < 0.01), and 6 h (105 +/- 5 versus 37 +/- 2 fmol/mg protein, p < 0.01) after endotoxin infusion. Its affinity decreased markedly (p < 0.05) at 6 h after the infusion. The contents of cortisol in plasma elevated at 0.5 h and remained at a high level until 4 h after the infusion. PLA2 activity rose from 97 +/- 25 to 188 +/- 12 U (p < 0.05), 99 +/- 13 to 285 +/- 25 U (p < 0.01), and 106 +/- 14 to 354 +/- 32 U (p < 0.01) at 2, 4, and 6 h after endotoxin infusion, respectively There was a negative correlation between the Bmax of GCR and PLA2 activity (r = -0.87, p < 0.01). The findings indicate that there was a secondary GCR abnormality and a higher PLA2 activity during endotoxin-induced lung injury. The glucocorticoid hypofunction caused by reduced GCR binding capacity may accelerate the pathologic response of acute lung injury. Therefore, in the early phase of ARDS, administration of a GCR protector or PLA2 inhibitor may be beneficial.
引用
收藏
页码:878 / 881
页数:4
相关论文
共 23 条
[1]  
ASHBAUGH DG, 1967, LANCET, V2, P319
[2]   CYTOPLASMIC-RECEPTOR FOR GLUCOCORTICOIDS IN LUNG OF HUMAN FETUS AND NEONATE [J].
BALLARD, PL ;
BALLARD, RA .
JOURNAL OF CLINICAL INVESTIGATION, 1974, 53 (02) :477-486
[3]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[4]   INCREASED SHEEP LUNG VASCULAR-PERMEABILITY CAUSED BY ESCHERICHIA-COLI ENDOTOXIN [J].
BRIGHAM, KL ;
BOWERS, RE ;
HAYNES, J .
CIRCULATION RESEARCH, 1979, 45 (02) :292-297
[5]  
DEMLING RH, 1990, CIRC SHOCK, V30, P297
[6]  
DEMLING RH, 1981, CIRC SHOCK, V8, P351
[7]   THE ROLE OF MEDIATORS IN HUMAN ARDS [J].
DEMLING, RH .
JOURNAL OF CRITICAL CARE, 1988, 3 (01) :56-72
[8]   ACUTE LUNG INJURY INDUCED BY PHOSPHOLIPASE-A2 - STRUCTURAL AND FUNCTIONAL-CHANGES [J].
EDELSON, JD ;
VADAS, P ;
VILLAR, J ;
MULLEN, JBM ;
PRUZANSKI, W .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1991, 143 (05) :1102-1109
[9]   RESPIRATORY-FAILURE AFTER ENDOTOXIN INFUSION IN SHEEP - LUNG-MECHANICS AND LUNG FLUID BALANCE [J].
ESBENSHADE, AM ;
NEWMAN, JH ;
LAMS, PM ;
JOLLES, H ;
BRIGHAM, KL .
JOURNAL OF APPLIED PHYSIOLOGY, 1982, 53 (04) :967-976
[10]   INCIDENCE AND OUTCOME OF THE RESPIRATORY-DISTRESS SYNDROME IN GRAM-NEGATIVE SEPSIS [J].
KAPLAN, RL ;
SAHN, SA ;
PETTY, TL .
ARCHIVES OF INTERNAL MEDICINE, 1979, 139 (08) :867-869