Expression And Interference Of Apoptosis-related Factors Bcl-2, Bax In Experimental Cerebral Vasospasm

Objective:To establish a modification subarachnoid hemorrhage (SAH) model and explore the role of morphology changs and expressions of apoptosis-related factors Bcl-2 and Bax in experimental cerebral vasospasm and its interference.Methods:This experimental study were divided into two parts. In the first part, twenty SD rats were randomly divided into tradition group(n=10) and modification group(n=10). SAH model was produced by injecting autologous arterial blood into the cisterna magna twice at 48h interval in rats. Tradition group presented with typical method, and modification group with improvement method. In the second part, ninety-six animals which were successfully modeled with improved were randomly divided into group A (SAH only, n=30), group B (SAH+NS, n=30), group C (SAH+cinepazide maleate, n =30), each group then divide into five subgroups (1d,3d,5d,7d,9d), group D (normal control group, n=6). Animals in the groups were killed at days 1,3,5,7 and 9 after the establishment of the models. Basilar arteries(BA) were stainned by hematoxylin-eosin for measurements of mean basilar artery cross-sectional areas, arterial diameter and observation of structures respectively. Protein of Bcl-2, Bax and cerebral vessels endothelial cell apoptosis in BA were evaluated by immunohistochemically stainned. The average of IOD values were calculated by Imge-proplus(Ipp) software. Then statistical comparisons were performed using SPSS 13.0.Results:1. This modified model had increased the survival rate in animals, and was more suitable in SAH.2. HE stainned:The pathological alterations of different time points after SAH were showed in group A, group B and group C. For group A, cerebral vasospasm was observed on day 3, and reached the peak on day 5, but cerebral vasospasm was attenuates on day 5 in group C. Group B was similar to group A. 3. Following SAH in group A and group B, the luminal diameter of cerebral arteries began to decrease on day 3, The luminal narrowing was the smallest on day 5, and were significantly less than group C and group D (P<0.05).4. The mean cross-sectional area of BA was the smallest in group A and group B on day 5, which compared with group C(P value<0.01), and maintained until the day 9.5. In group A and group B, the expressions of Bcl-2 reduced on day 3, and Bcl-2 proteins levels (IOD) was the lowest on day 5. But the expressions of Bcl-2 positive cells in group C were began to increase significantly on day 3 and maintained until on day 7, day 9, Its IOD values achieved a peak on day 5, This was statistically significant at p <0.01(compared with group A and group B).6. In group A and group B, the expressions of Bax positive cells increased significantly on day 3. Its IOD values achieved a peak on day 5, But the expressions of Bax reduced gradually until on day 9. This was statistically significant at p<0.01 (compared with group C and group D).Conclusion:1. The modification model is reliable to perform and may be useful for investigating the pathophysiology of SAH.2. Our results suggested that cerebralvascular cell apoptosis in the basilar arteries of rats may associate with cerebral vasospasm after SAH.3.Cinepazide maleate can be efficiently attenuated SAH-induced cerebral vasospasm.