Effect of TLR-4 and HO-1 on acute lung injury induced by hemorrhagic shock in mice

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Abstract

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<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<0.01 or P<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<0.01 or P<0.05), and the W/D, MPO in C3H/ HeJ mice were obviously lower in Hem 24 h (P<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.

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Chen, C., Wang, Y. L., Wang, C. Y., & Zhang, Z. Z. (2008). Effect of TLR-4 and HO-1 on acute lung injury induced by hemorrhagic shock in mice. Chinese Journal of Traumatology - English Edition, 11(2), 78–83. https://doi.org/10.1016/S1008-1275(08)60017-6

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