Effect of TLR-4 and HO-1 on acute lung injury induced by hemorrhagic shock in mice.
OBJECTIVE
To examine whether TLR-4 has an effect on hemorrhage induced changes in lung, and to investigate the change of heme oxygenase-1 (HO-1) on acute lung injury (ALI) induced by hemorrhagic shock in mice.


METHODS
Forty-eight male mice, including C3H/HeN mice and C3H/HeJ mice, were randomly divided into sham group (n=12), hemorrhagic shock group with twelve mice in each phase. Blood pressure (BP) was monitored continuously by attaching carotid artery catheter to a strain gauge pressure transducer/ polygraph. Arterial blood samples were taken for blood gas analysis. A mouse model of non-lethal hemorrhagic shock and resuscitation was used to observe pulmonary myeloperoxidase (MPO) activity and wet/dry weight ratio (W/D). The expression of HO-1 was observed by means of RT-PCR and immunohistochemistry. IL-6 and IL-10 in lung tissue homogenate were assayed by enzyme-linked immunosorbent assay (ELISA). The pulmonary pathologic changes were observed under electron microscope and light microscope.


RESULTS
Compared with sham group, the expression of HO-1 in lung tissue was significantly higher in Hem 24 h and Hem 48 h of C3H/HeN mice (P less than 0.01). The expression of HO-1 mRNA and the levels of IL-6, IL-10 and MPO in lung tissue were markedly increased in Hem 24 h (P less than 0.01 or P less than 0.05); Compared with C3H/HeN mice, the expression of HO-1 mRNA and the levels of IL-6 and IL-10 in C3H/HeJ mice significantly decreased in Hem 24 h and Hem 48 h (P less than 0.01 or P less than 0.05), and the W/D, MPO in C3H/HeJ mice were obviously lower in Hem 24 h (P less than 0.05). The injuries of lung tissues after hemorrhagic shock have been demonstrated by histological examination with electron microscope and light microscope.


CONCLUSIONS
TLR-4 and HO-1 might modulate the balance of pro- and anti-inflammatory processes in inflammatory reaction of hemorrhagic shock-induced ALI, and the activation of Toll-like receptor might induce the transcription activity of HO-1, which may play a key role in acute lung injury.
Chen
Chang
C
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Wang
Yan-lin
YL
Wang
Cheng-yao
CY
Zhang
Zong-ze
ZZ
D000208:Acute Disease; D000818:Animals; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D051197:Toll-Like Receptor 4; D051547:Heme Oxygenase-1