[Effects of different doses of hydrocortisone on acute lung injury in rats with early septic shock induced by Escherichia coli].
OBJECTIVE
To observe the effects of different doses of hydrocortisone (HC) on acute lung injury (ALI) and inflammatory response in rats at early stage of septic shock induced by Escherichia coli and to investigate the possible mechanisms for such differences.


METHODS
ALI model of early septic shock was induced in rats by two injections of Escherichia coli at 5 hours interval, with the first intraperitoneal injection of 6.50 x 10(10) cfu/kg and followed by an external jugular vein injection of 2.00 x 10(11) cfu/kg. Forty Wistar rats were randomly divided into the following five groups: normal control, ALI without HC treatment, high-dose HC (150 mg/kg), medium-dose HC (20 mg/kg) and low-dose HC (6 mg/kg). Two hours after the treatment, the specimens were collected for histopathological examination and the biological indexes of lung injury were measured. The expressions of intercellular adhesion molecule-1 (ICAM-1) and glucocorticoid receptor (GR) in lung tissues were also investigated by immunohistochemical assays.


RESULTS
The biological indexes of lung injury [wet/dry weight ratio (g/g), total protein concentration in bronchoalveolar lavage fluid (mg/L) and lung permeability index (10(-3))] in ALI group (4.76 +/- 0.10, 278.96 +/- 60.45, 4.73 +/- 0.60) were significantly increased as compared to those in normal control group (4.10 +/- 0.07, 67.46 +/- 13.27, 1.12 +/- 0.15) (P < 0.05). The grades of ALI pathologic changes in ALI group (11.13 +/- 1.13) was significantly higher than that in the normal control group (0.50 +/- 0.53, P < 0.05). The ratio of expression area of ICAM-1 in ALI group (0.149 +/- 0.037) was significantly increased as compared to that in the normal control group (0.051 +/- 0.018) (P < 0.05). The ratio of expression area of GR all group (0.043 +/- 0.037) was significantly decreased as compared to that in the normal Control group (0.124 +/- 9.040) (P < 0.05) After administration of HC, all the lung injury indexes, pathological grades and the ratios of expression area of ICAM-1 and GR were significantly improved, with the most remarkable effects observed in the low-dose HC group. The expressions of ICAM-1 and GR showed a significantly negative linear correlation (r = 0.55, P < 0.0001).


CONCLUSIONS
These results indicated that the low-dose HC treatment had the most remarkable effects of improving the biological indexes of lung injury, inflammatory mediators and pathological changes. These HC dose dependent therapeutic effects might be associated with the level of GR expression.
Zhou
Tao
T
Department of Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital University of Medical Sciences, Beijing 100045, China.
Fan
Xun-mei
XM
Wang
Yong-qing
YQ
Qi
Yu-jie
YJ
Chen
Hui
H
Qian
Su-yun
SY
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006854:Hydrocortisone / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018799:Intercellular Adhesion Molecule-1; D006854:Hydrocortisone