| Background: The carbon monoxide (carbon monoxide, CO) is one kind of a colorless, tasteless, not smelly, the nonirritating toxic gas, which is the most common asphyxiating gas causes toxic death in the life and the production. It may cause organism multi-system harm, that the cerebrum is worst. Especially delayed encephalopathy after carbon monoxide poisoning (DEACMP) will happen to some people after carbon monoxide poisoning. The clinical manifestation is a group by the acute stupid primarily energetic nerve function disorder, which is the most serious type in CO poisoning. There are many kinds of hypotheses about DEACMP, until now the clear pathogenesis of the disease has not been discovered. The related CO poisoning and the DEACMP pathogenesis research and some hypotheses were proposed, but they are still not extremely clear. At present, the animal experimentation confirmed that the angiogenesis after the cerebral ischemia. But there was not explicit reported about the angiogenesis after the CO poisoning. Angiopoietin belong to a specific vessel growth factor acting on vascular endothelial cells, until now there are 4 members that already discovered in the angiopoietin family (Angl-4). Ang-1 and Ang-2 play important roles in process of angiogenesis, which ligand for the endothelial-specific receptor tyrosine kinase, Tie-2. Foreign research speculated that in ischemic and hypoxia condition, Ang/Tie-2 system act on vascular endothelial cells, smooth muscle cells, pericytes regulating their interaction, promoting vesselsto sprout and remodel, enhanceing the cerebral blood flow in ischemic focus.Objective: The project is on the basis of carbon monoxide poisoning model of mouse, to observe expression of Ang-1, Ang-2 and Tie-2 in mouses'brain and brain pathological change at the just time, provide new ideas for prevention and treatment to clinical acute carbon monoxide poisoning and DEACMP.Methods: 108 healthy Kunming male mouse, were divided into Air control group, Carbon monoxide poisoning group, 54 mice in every group. Each group is divided into nine sub-group. as follows:6h,1d,2d,3d, 4d,7d,14d,21d,28d group,6 mice in every group. Carbon monoxide poisoning model of mouse was established with intraperitoneal injection. We check the brain tissue of mouse in each group according to every time point. Observing the ultrastructure of capillary endothelial cells by electron microscopy. Observing neovascularization of mouse tissue by HE, count the formation of vascular cavities and no significant muscular vessel wall of the microvessel count.All datas were expressed by mean±sd, statistical analysis software of SPSS13.0 t-test was employed.Result:1. By light microscope, we can see brain edema, increased perivascular space, nerve cells around the gap widened, partial of neuronal apoptosis. In 4d the hippocampu area of CO poisoning group mice appears the few irregular capillaries and 14d to the peak, in 21d mouse's hippocampu area vessel obviously become the strip funicular, the correspondence appears the lumen expansion. In 28d capillaries reduced. 6h, 1d, 2d and 3d groups are no significant different with the control group. The rest of the time points are different statistically with the control group. (P<0.05).2. The Ang-1 show accidental and fragmentary expression in the air control group. Ang-1 in the hippocampu area of CO poisoning group mice in 6h reach to the first peak, drops gradually, but still was higher than the level of air control group, the second peak is 7d, and dropped once more. It would reduce obviously to 28d, From 6h to 28d , the CO poisoning group and air control group's difference had statistics significance (P<0.01).3. The expression of Ang-2 is extremely low in the air control group. Ang-2 in the hippocampu area of CO poisoning group mice presents two stages changes, it expressed upward to a high level in 6h after CO poisoning, the first peak appears in 1d, drops gradually, which is still higher than the air control group level, 7-14d appears to the second peak once more, It would reduce obviously to 28d, From 6h to 28d , the CO poisoning group and air control group's difference had statistics significance (P<0.01).4. The Ang-2 /Ang-1 in the 6h-1d and 4-14d presents rise tendency, 1-4d and 14-28d presents drop tendency in CO poisoning group.5. Tie-2 is few expressions in the air control group. Tie-2 in the hippocampu area of CO poisoning group presents two stages changes, it expressed upward to the high level in 6h after CO poisoning, the peak appears in 1d and 7d, 21d drops obviously. From 6h to 28d , the CO poisoning group and air control group's difference had statistics significance (P<0.01).Conclusion:1. Ang-1, Ang-2 and Tie-2 in the protein level express obvious markup in mice's hippocampu area after the CO poisoning, which presents two stages changes, the second peak may possible correlate to the DEACMP.2. The Ang/Tie-2 system participated in the angiogenesis after CO poisoning... |
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