大鼠脑出血灶周HIF-1α和COX-2的动态变化

摘要

目的 观察大鼠脑出血后血肿灶周脑组织中HIF -1α、COX -2蛋白的动态表达,探讨二者与脑水肿的关系,以及HIF -1α和COX -2蛋白的表达在血肿灶周脑组织损伤中的作用机制.方法 SD大鼠35只,随机分为假手术组、脑出血6h、1、3、7、14、21天组,每组5只.采用自体血体内注射法建立脑出血动物模型,用免疫组化法检测脑出血后血肿灶周脑组织中HIF -1α和COX -2蛋白的动态表达,并用干/湿比重法测定脑含水量.结果 脑出血后6h HIF - 1α、COX -2蛋白的表达和脑水含量明显升高,3～7天达到高峰,第14天明显降低,COX -2及脑水含量在21天基本降至正常.HIF - 1α在21天仍有较高水平的表达.造模后6h,脑出血组与假手术组相比,HIF -1 α及COX -2蛋白的表达和脑水含量明显增高,其差异有统计学意义(P＜0.05).脑出血组的各时间点间比较,其差异均有统计学意义(P＜0.05).HIF - 1α蛋白的表达与脑水含量呈正相关(r =0.636,P＜0.01)；COX -2蛋白的表达与脑水含量呈正相关(r=0.927,P＜0.01).结论 大鼠脑出血后血肿灶周HIF -1α、COX -2蛋白的表达呈一定的变化规律.随着脑出血时间的延长HIF -1α蛋白、COX -2蛋白的表达程度和脑组织水肿程度呈正相关.%Objective To investigate the dynamic changes of HIF-lot and COX-2 protein in perihematoma after Intracerebral hemorrhage in rats, to analysis their correlation with the time of ICH and brain edema, and try to explore the mechanism of action of the expression HIF-lα and COX-2 protein on the brain tissue injury. Methods Thirty-five healthy SD rats were randomly divided into sham operation group (n=5) and ICH model groups (n =30). Rats were sacrificed at 6h,1days,3days,7days, 14days and 21 days after operation, respectively. The expressions of HIF-1α and COX-2 were investigated using immunohistochemistry, Brain water content was measured by the wet/dry specific gravity method. Results HIF-1α, COX-2 protein expression and brain water content was increased over time in ICH model groups (P＜0.05), The peak value appeared at 3days to 7days, and began to decline obviously at 14days, and then COX-2 protein expression and brain water content went back to normal level at 21 days, HIF-la still had high expression at 21 d. Compared with sham operation group, the HIF-lα and COX-2 protein expression and brain water content was increased obviously after building the model 6h in Cerebral hemorrhage group,and the difference was statistically significant (P＜0.05), There was positive correlation between HIF-lα protein and brain water content by Pearson's correlation coefficient (r = 0. 636, P＜0. 01). There was positive correlation between COX-2 protein and brain water content by Pearson's correlation coefficient (r =0. 927, P＜0. 01) . Conclusion In ICH model groups, the changes of HIF-lα and COX-2 protein expression have certain rules. With the extension of time, there was positive correlation between HIF-lα protein and brain water content. There was positive correlation between COX-2 protein and brain water content.