阿托伐他汀对慢性脑低灌注大鼠海马ADAM10的影响

Effect of atorvastatin on ADAM10 in hippocampus of chronic cerebral hypoperfusion in rats

目的探讨慢性脑低灌注老龄大鼠学习记忆功能、海马解聚索和金属蛋白酶10（a disingtergrin and metalloprotease 10, ADAM 10）mRNA表达变化以及阿托伐他汀对其的影响。方法72只健康雄性Wistar老年大鼠随机分为假手术组、脑低灌注组和阿托伐他汀处理组。制作永久性双侧颈总动脉闭塞（two—vessd occlusion，2VO）模型。阿托伐他汀处理组术后用阿托伐他汀10mg（kg·d）灌胃。采用实时荧光定量聚合酶链反应在模型制作后1、2、4和16周检测双侧海马ADAM10 mRNA表达。结果从模型制作后2周开始，脑低灌注组学习记忆功能较假手术组显著下降（P〈0．05），模型制作后4周和16周时进一步下降（P〈0．01）；阿托伐他汀处理组模型制作后1周、2周和4周时学习记忆功能与脑低灌注组无显著差异，但16周时较脑低灌注组显著改善（P〈0．01）。与假手术组相比，脑低灌注组模型制作后各时间点海马ADAM10 mRNA表达分别下调22％、43％、35％和50％（P均〈0．01），阿托伐他汀处理组海马ADAM10 mRNA的表达在2周时较脑低灌注组增高22％（P〈0．05），其余时间点无显著差异。结论慢性脑低灌注可导致老龄大鼠海马ADAM10 mRNA表达下调，阿托伐他汀在早期可抑制ADAM10 mRNA表达下调。

Objective To investigate the learning and memory functions, expression changes of disintegrin and metalloprotease 10 （ADAM10） mRNA in hippocampus in the aged rats with chronic cerebral hypoperfusion as well as the effect of atorvastatin on them. Methods A total of 72 rats were randomly divided into sham operation, cerebral hypoperfusion and atorvastatin treatment groups. A permanent bilateral common carotid artery occlusion （2VO） model was induced. Atorvastatin 10 mg/（kg · d） was administered orally after procedure in the atorvastatin treatment group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ADAM10 mRNA in bilateral hippocampus at 1, 2, 4, and 16 weeks after modeling, Results Two weeks after modeling, the learning and memory functions were decreased significantly in the cerebral hypoperfusion group compared to the sham operation group （P 〈 0. 05）. At 4 and 16 weeks after modeling, they were further decreased （P 〈 0. 01）; there were no significant differences in the learning and memory functions at 1, 2, and 3 weeks after modeling between the atorvastatin treatment group and the cerebral hypoperfusion group, however, they were improved significantly at 16 weeks compared to the cerebral hypoperfusion group （P〈 0. 01）. The expression of ADAM10 mRNA in hippocampus at different time points after modeling in the cerebral hypoperfusion group was down-regulated by 22%, 43%, 35%, and 50%, respectively compared to the sham operation group （all P 〈0. 05）. The expression of ADAM10 mRNA in hippocampus at 2 weeks in the atorvastatin treatment group was higher than 22% in the cerebral hypoperfusion group （P 〈 0. 05）. There were not significant differences at other time points. Conclusions Chronic cerebral hypoperfusion results in the down-regulation of the expression of ADAM10 mRNA in hippocampus in the aged rats, and atorvastatin may inhibit down-regulation of the expression of ADAM10 mRNA at early stage.