二甲胺四环素在蛛网膜下腔出血中保护作用的研究

Objective To investigate the effect of minocycline on early brain injury (EBI) following subarachnoid hemorrhage(SAH) in rats. Methods SAH was induced by the filament perforation model in male Sprague Dawley rats. SD rats(n=77) were randomly assigned to sham (n=22), SAH+vehicle (n=28), and SAH+minocycline (n=27) groups. Minocycline (135mg/kg) or equal volume of vehicle was administered 1 h after SAH induction. Mortality, neurological scores, brain edema were evaluated 24 h after SAH. Cell apoptosis were examined by TUNEL staining, and the expression of caspase-3 and Bcl-2 was assayed by Western blot at the same time point. Results The mortality was 21.4% in SAH+vehicle group, 18.5% in the SAH+minocycline group, while no death was observed in sham-operated rats; there was no significant difference in mortality between SAH+vehicle and SAH+minocycline groups (P＞0.05), but the mortality in these two groups was much higher than that in shamgroup(P＜0.05). The water content of brain was significantly increased in the SAH+vehicle group (80.00±0.16)% compared with that in sham group [(79.13±0.08)%, P＜0.05]. Minocycline treatment markedly reduced brain water content (79.36±0.07)% compared with that in SAH+vehicle group (P＜0.05). Caspase-3 levels were markedly increased in SAH+vehicle group (1.53±0.24) compared with sham group (1.00±0.21). Minocycline treatment significantly reduced caspase-3 levels, compared to SAH+vehicle group (1.11±0.18, P＜0.05). A significant decrease in Bcl-2 expression was observed in SAH+vehicle group(0.65±0.03) compared with the sham group (1.00±0.12). The treatment of minocycline upregulated the expression of Bcl-2,compared to SAH+vehicle group (0.93±0.13, P＜0.05). TUNEL-positive cells were increased in the cortex of SAH+vehicle rats,compared to sham group [(31.50±3.70)%, P＜0.05]. Minocycline treatment significantly reduced the number of TUNEL positive cells, compared to SAH+vehicle group [(14.25±2.50)%, P＜0.05]. Conclusion Minocycline may reduce early brain injury after subarachnoid hemorrhage in rats by inhibiting cell apoptosis, which is associated with down-regulation of caspase-3 and up-regulation of Bcl-2.