Effects Of Midazolam On The Vascular Endothelial Growth Factor In Mongolia Gerbil Following Cerebral Ischemia-reperfusion

Objective: 1.To clarify the chronological expression of VEGF, malondialdehyde (MDA) and superoxide dismutase (SOD) in experimental total cerebral ischemia-reperfusion and the possible mechanisms.2.To clarify the effects of midazolam on VEGF,SOD and MDA in Mongolia gerbil following total cerebral ischemia-reperfusion injury, as well as the new clinical application of midazolam. Methods:144 male Mongolia gerbil were randomly divided into three groups: the sham-operated group(A) 48 cases, the operated group (B) 48 cases and the midazolam group (C) 48 cases. These groups were divided into 4 time points of 6 hours, 1 days, 3 days and 7 days with 36 animals of each time points. Total cerebral ischemic Mongolia gerbil model was established by two-artery methods. When reperfusion began, the group C gerbil were administered via intraperitoneal injection with 5mg/kg of midazolam, the group B gerbil were administered via intraperitoneal injection with 50ml/kg. Then items below should be observed:1. Evaluation of ethology after 7d reperfusion with open-field test.2. Positron emission tomography imagines were measured after 6h, 1d, 3d and 7d reperfusion.3. The level of malonic dialdehyde (MDA) and superoxide dismutase (SOD) in brain were measured with absorption spectrometry.4. The expression of VEGF in cerebral tissue was observed by immunohistochemistry technique and western-blot technique. Results:1. The exploration of gerbil was obviously increased. Compared with group A, the number of grids gerbil creped increase 55% in group B after 7d reperfusion, and difference was significant(p<0.01). For group C and group A, the difference was significant(p<0.01). Compare with group B, the number of grids gerbil creped decrease obviously in group C (p<0.01).2. Positron emission tomography imaginesThere was no apparent abnormality in sham-operated group (group A). For group B and group C, brain's filling area was obviously decreased, and difference was significant (p<0.01). There was no difference between group B and group C at 6h after reperfusion, but other time points had significant difference(p<0.01).3. The level of MDA and SOD in brainFor group C, the level of MDA increased with the reperfusion continuing, and the level was reached the highest point at 1d after reperfusion. Then the content of MDA decreased. Compared with group A, the MDA level of group B and group C were all higher (except 7d); the diversity of MDA level for group C was similar to that of group B, but difference was significant(P<0.01).For group C, the level of SOD decreased with reperfusion continuing, and the level reached the lowest point at 1d after reperfusion. Then the content of SOD increased and back to normal till 7d. Compared with group A, the SOD level of group B and group C were all lower sharply; the diversity of SOD level for group C was similar to that of group B(except 6h).4. The expression of VEGF in total ischemic cerebralA number of VEGF positive cells express in group A gerbil. For group B, VEGF began to express at 6h after reperfusion, and reached climax at 3d, which the difference was significant (P<0.01) compared to that of 6h.VEGF expressed in glia cells, macrophages, neurocytes and vascular endothelial cells. For group C, the tendency of VEGF expression was same to that of group B, but the VEGF positive cells were more than group B, the difference was significant(P<0.01). The tendency of VEGF expression with immunohistochemistry technique was similar with western-blot technique, but the climax time at 1d in advance.Conclusion: VEGF play an important role of total cerebral ischemia-reperfusion injury. It is a critical period to the reconstitution of microcirculation from 24h to 72h in reperfusion period. For a large of endogenous VEGF is produced, it is profit the formation of new vessels. Therefore, it is great significant to improve the microcirculation of ischemia tissue and recover the blood-supply of injury neuron.1. Positron emission tomography imaging can rightly reflect the process of cerebral ischemia in vivo, and proof the volume of cerebral infarction decreased with injection of midazolam.2. Ischemical reperfusion injury cells capacity of antioxygen can be improved by midazolam.3. Endogenous VEGF can be increased by midazolam in the process of ischemiacal reperfusion.