| Backgroud: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 damage, that the cerebrum is worst. Especially delayed encenphalopathy 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 acute CO poisoning and DEACMP, until now the clear pathogenesis of the disease has not been discovered. These hypotheses include hypoxic-ischemic, cell toxic damage, reperfusion damage and occurrence of free radical, production of excitatory amino acids and apoptosis, and so on. Among the hypotheses, hypoxic-ischemic mechanism plays an important role in exploring the mechanism of brain injury of carbon monoxide poisoning. In recent years, many studies showed the existence of brain injury of neorascularization phenomenon in the surrounding region of ischemia. Vascularization might trigger the rebuilding of capillary vessel net in damage region, and to improve the hemoperfusion of microcirculation tissues. It is important for the survival of the hypoxic-ischenic neurons after CO poisoning. At present, animal experiments already confirmed the existence of brain injury of neorascularization phenomenon in hypoxic-ischemic regions, but it is not reported that Cerebrovascular pathological change after CO poisoning. During vascularization, angiopoiten (Ang) family plays an important role. In this family, Ang-1 and Ang-2 are closely associated with vascularization, and they can bind recepetor Tie-2 in surface of endothelial cell to enhance vascularization. During the final stage of vascularization, Ang/Tie-2 system play a role to influence the interaction of endothelial cell, smooth muscle cell and pericyte, thereby, to urge the vascularization and vascular remodeling. However, it is not known that dynamic changes of Ang-1, Ang-2 and Tie-2 mRNA levels in mice brain after carbon monoxide poisoning.Butylphthalide is a kind of new drug used to cure the acute cerebral accident in the clinical. Butylphthalide can enhance angiogenesis, improve cerebral blood supply, ameliorate microcirculation, protect chondriosome, and so on, and is involved with many stages of hypoxic-ischemic mecha-nism. Yet, it is not clear that the mechanism of Butylphthalide curing and improving CO poisoning damages.Objective:The project is on the basis of carbon monoxide poisoning model of mice, to observe changes of Ang-1, Ang-2 and Tie-2 mRNA levels in mice brain and to approach influence of endothelial system against CO poisoning, and explore effectiveness of vascularization mechanism in brain damage; At the same times, to study protection effect of Butylphthalide curing CO poisoning in molecule level, and to try to provid a rationale and thinking of improving CO poisoning and preventing DEACMP.Methods:144 healthy Kunming male mice, were divided into Air control group, Carbon monoxide poisoning group and Butylphthalide group, 48 mice in every group. Each group was divided into eight sub-group, as followed:6h, 1d,2d,3d,4d,7d,14d,28d,6 mice in every group. Carbon monoxide poisoning models of mice were established with intraperitoneal injection. We checked the brain tissues of mice in each group according to every time point. Observing changes of Ang-1, Ang-2 and Tie-2 mRNA levels in mice brain by RT-PCR method. All datas were presentated by mean±SD, statistical analysis software of SPSS 16.0 One-Way ANOVA was employed.Rusult:1. After carbon monoxide poisoning, Ang-1, Ang-2 and Tie-2 mRNA levels showed an increase with two peaks, respectively in 3 day (7.02±0.11,7.67±0.22 and 8.73±0.07, P＜0.05 comparing with control) and 7 day (6.60±0.36,7.99±0.06 and 7.69±0.05, P＜0.05 comparing with control), the results showed Ang/Tie-2 system quickly reconstruct and restore blood vessel of damage regions.2. After use of Butylphthalide, Ang-1, Ang-2 and Tie-2 mRNA levels showed an increase with one peak in 3 day (6.04±0.35,8.46±0.11 and 10.66±0.11, comparing with CO group, P< 0.05), moreover, mRNA levels earlier increased than those of CO group. The results showed Butylph-thalide efficaciously protected the mice brain.3. Results of Ang-2 to Ang-1 showed Ang-2/Ang-1 remained a low level in control group (0.36±0.03), and in CO group, Ang-2/Ang-1 rised a peak in 6h point (comparing with control, P<0.05); In 2d point, Ang-2/Ang-1 got to the lowest level, subsequently, Ang-2/Ang-1 slowly moved and reached another peak (comparing with control, P<0.05), and in 14d point, Ang-2/Ang-1 is normal; in Butylphthalide group, Ang-2/Ang-1 also rised a peak in 6h point (comparing with CO group, P< 0.05); In 1d-2d point, Ang-2/Ang-1 got to the lowest level, subsequently, Ang-2/Ang-l slowly moved and reached another peak in 4d-7d (comparing with CO group, P< 0.05), and in 28d point, Ang-2/Ang-1 is normal.Conclusion:1. After carbon monoxide poisoning, Ang-1, Ang-2 and Tie-2 mRNA levels in the brain showed an increase with two peaks, and it suggested that DEACMP might happen. Ang/Tie-2 system in cerebrovascular endothelial cell showed up the regular changes, and played an important role to reconstruct and restore vessels.2. Butylphthalide could enhance angiogenesis, improve cerebral blood supply and ameliorate microcirculation, so Butylphthalide might cure and improve CO poisoning damages and prevent DEACMP.
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