阿托伐他汀预处理对脑缺血再灌注大鼠基质金属蛋白酶9表达的影响

Effect of atorvastatin pretreatment on MMP-9 expression in I/R rats

目的观察阿托伐他汀对大鼠脑缺血再灌注后基质金属蛋白酶9(MMP-9)表达的影响。方法选择SD大鼠96只,随机分为:假手术组16只,脑缺血再灌注组40只,阿托伐他汀组40只。建立大脑中动脉缺血2h再灌注模型。阿托伐他汀组在建立模型前21d予以阿托伐他汀灌胃。假手术组分为24h和48h,每个时间点8只。缺血再灌注组和阿托伐他汀组根据缺血再灌注时间分为3、12、24、48、96h,每个时间点8只。于各个时间点进行神经行为学测试;TTC染色测定缺血体积;免疫组织化学SABC法测定MMP-9蛋白的表达变化;RT-PCR法对各组脑组织中MMP-9mRNA表达进行分析。结果与缺血再灌注组比较,阿托伐他汀组3、12、24、48、96h神经功能评分明显降低,梗死体积明显减小[(102.37±10.31)mm3 vs(135.26±12.16)mm3,(105.78±9.23)mm3 vs(155.07±14.12)mm3,(110.56±13.45)mm3 vs(162.47±11.41)mm3,(119.71±10.01)mm3 vs(180.27±14.27)mm3,(121.63±11.23)mm3 vs(193.41±11.56)mm3,P<0.05];12、24、48、96h MMP-9蛋白、mRNA表达显著降低,差异有统计学意义(P<0.05)。结论脑卒中前预服用阿托伐他汀可能通过降低MMP-9水平来达到脑保护的效果。

Objective To study the effect of atorvastatin on MMP-9expression in I/R rats.Methods Ninety-six SD rats were randomly divided into sham operation group（n=16）,I/R group（n=40）and atorvastatin treatment group（n=40）.A middle cerebral artery I/R model was established.Rats in atorvastatin treatment group were treated with oral atorvastatin 21 days before I/R model was established.Rats in sham operation group were further divided into 24 hgroup and 48 h group and those in I/R group and atorvastatin treatment group were further divided into 3,12,24,48,96hgroups（8in each group）.Their neurological behaviors were detected at different time points.Ischemia size was measured with TTC staining.MMP-9and MMP-9 mRNA expressions were detected by RT-PCR with immunohostochemical SABC staining.Results The neurological function score was significantly lower,the infarction size was significantly smaller,and the MMP-9and MMP-9 mRNA expression levels were significantly lower in atorvastatin treatment group than in I/R group at different time points（P〈0.05）.Conclusion Atorvastatin treatment before ischemic stroke can protect brain against I/R injury by down-regrulating the MMP-9expression level.