Effects of recombinant human growth hormone on acute lung injury in endotoxemic rats.
OBJECTIVE
To investigate the effects of recombinant human growth hormone (rhGH) on rat acute lung injury (ALI).


METHODS
ALI was mimicked by intraperitoneal (i. p.) injection of E. coli. Female Sprague-Dawley rats were randomized into three groups: control group, injected with physiologic saline (i. p.); ALI group, received a bolus injection of E. coli (1 x 10(10) cfu/l, 15 ml/kg, i. p.) followed by intramuscular physiologic saline injection; and ALI + GH group, received a bolus administration of E. coli, and then treated with intramuscular rhGH injection (2.25 U/kg/d). ALI group and ALI + GH group were subdivided into day 1 and day 3 subgroups, respectively. Left lungs were lavaged and bronchial alveolar lavage fluid (BALF) was harvested. Lung injury score, lung wet-to-dry weight (W/D) ratio, percentage of neutrophils (PMNs) in BALF, lung permeability index (LPI), intercellular adhesion molecule-1(ICAM-1) expression and activation of nuclear factor-kappa B (NF-kappaB) in the lungs were determined.


RESULTS
(1) On day 1 and day 3, the lung injury score, lung W/D ratio, LPI and protein content in BALF were significantly higher in the ALI group than in the control and ALI + GH groups. rhGH attenuated lung injuries significantly. (2) Compared with the control group, the percentage of PMNs in BALF was elevated significantly in the ALI and ALI + GH groups, especially in ALI group. (3) Nuclear positive rate of NF-kappaB and ICAM-1 expression at the levels of protein and mRNA in the lung in the ALI group on day 1 and day 3 were higher than in the control group. rhGH diminished activation of NF-kappaB and expression of ICAM-1 in the lung markedly.


CONCLUSIONS
Treatment with rhGH can significantly attenuate lung injury in the endotoxemic rats, which may be attributed to the reduction of the expression of ICAM-1, the influence on the adhesion and activation of PMNs, the inhibition of the activation of NF-kappaB and the regulation of the transcription of certain proinflammatory cytokines.
Yi
C
C
Cancer Center, Huaxi Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China. yicheng6834@163.com
Wang
S R
SR
Zhang
S Y
SY
Yu
S J
SJ
Jiang
C X
CX
Zhi
M H
MH
Huang
Y
Y
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019446:Endotoxemia / Q000150:complications* / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000150:complications* / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology*
D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D018799:Intercellular Adhesion Molecule-1