ABSTRACT
<p><b>OBJECTIVE</b>To elucidate the pathogenic role of leukotriene B4 (LTB4) in increased pulmonary microvascular endothelial cell permeability induced by one lung ventilation (OLV) in rabbits.</p><p><b>METHODS</b>Forty-eight healthy Japanese white rabbits were randomly divided into control group (group C), saline pretreatment group (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV group (group SO) and bestatin plus saline pretreatment with OLV group (group BO). ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and phospholipase Cεl (PLCEl) expressions were examined by Western blotting and quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in the lung tissues were determined to evaluate the permeability of the pulmonary microvascular endothelial cells (PMVECs). The severities of lung injury were evaluated by lung histomorphological scores.</p><p><b>RESULTS</b>No significant differences were found among groups C, S and B except that LTA4H expressions was significantly lower in group B than in groups C and S (P<0.05). OLV significantly increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05).</p><p><b>CONCLUSION</b>Bestatin plays a protective role in OLV-induced rabbit lung injury by downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV-induced lung injury.</p>
ABSTRACT
Objective: To observe the effects of ischemic postconditioning (PC) on changes of cerebral water content, cerebral blood flow, infarct area and hippocampal ultrastructural, and to explore the neuroprotective mechanisms of ischemic PC on undergoing thrombotic cerebral ischemic injury. Methods: Tree shrews were randomly grouped into control, ischemia 4 hours, ischemia 24 hours, ischemic postconditioning 4 hours and ischemic postconditioning 24 hours (n = 8) Eight animals were used for HE staining(n = 3) and electron microscopy(n = 5). The model of thrombotic cerebral ischemia was induced by photochemistry in tree shrews. Four hours after the model establishment, the common carotid artery on the ischemia side was clamped for 5 minutes, then perfused by removing the clamp for 5 minutes, and repeated the same management 3 times, so that the model of PC was established. The changes of the brain water content of local cortex were measured by Elliott dry-wet weight and the brain infarct area was determind by 2,3,5-triphenyl-tetrazolium chloride staining. In addition, the regional cerebral blood flow of local cortex was measured by laser doppler, and the ultrastructural changes in the CA1 area of hippocampus in different groups were observed under an electron microscope. Results: More neuron pycnosis was observed in hippocampal CA1 area. Obvious swelling of mitochondria, partial disrupt and vanish of the mitochondria cristae and more endoplasmic reticulum cisterna appeared in the neuron of hippocampus at the 24th hour after cerebral ischemia. With the time prolonging of ischemic, the brain water content was significantly increased (86. 81% ± 1. 08%) in the ischemia group at the 24th hour compared with sham group. Cerebral infarction area was maximum (33.00% ±3.03%) and regional cerebral blood flow decreased obviously [(134. 27 ±28.75) ml/min]. The brain water content was significantly decreased (81. 04% ± 1. 04%, P <0. 01) and the infarct area was significantly shrink in ischemic postconditioning group (16. 79% ± 1. 29%, P < 0. 01) than that in ischemia group. The regional cerebral'blood flow in ischemic postconditioning group was in contrast to ischemia group significantly at the 24th hour [(195. 25 ±21. 18) ml/min, P<0.01]. Conclusion: Ischemic postconditioning attenuates the edema in ischemic brain and narrow the cerebral infarction area in tree shrews. The mechanism may be related to the improvement of local cerebral blood flow.