ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Male , Mice , Acute Disease , Heme Oxygenase-1 , Metabolism , Lung , Pathology , Mice, Inbred C3H , Random Allocation , Shock, Hemorrhagic , Toll-Like Receptor 4 , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-kappaB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.</p><p><b>METHODS</b>Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n = 8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-alpha were measured by ELISA, and the heart was harvested for determination of NF-kappaB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.</p><p><b>RESULTS</b>After reperfusion, NF-kappaB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-alpha were significantly increased in Group II, compared with Group I (P < 0.01), and they were markedly reduced in Group III, compared with Group II (P < 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.</p><p><b>CONCLUSIONS</b>Shenfu injection inhibits NF-kappaB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.</p>