米诺环素对脑缺血再灌注后明胶酶活性及血脑屏障影响的研究

Effects of minocycline on the activity of gelatinases and the blood-brain barrier following transient focal cerebral ischemia

目的探讨米诺环素对大鼠局部脑缺血再灌后血脑屏障损伤的影响及其作用机制。方法28只Wistar大鼠分为假手术组、缺血再灌注组、米诺环素组和生理盐水组。运用磁共振成像监测缺血再灌后血脑屏障损伤及梗死体积的变化,再灌注24h后进行神经功能缺陷评分和脑组织明胶酶活性测定。结果缺血再灌后3.5h及24h,米诺环素组DWI、T2WI上异常高信号体积,T1WI增强扫描的信号强化范围、信号强度均明显低于缺血再灌注组和生理盐水组(P<0.05);与后两组相比,米诺环素组神经功能缺陷评分及脑组织明胶酶活性亦显著降低(P<0.05)。结论米诺环素能显著减轻缺血再灌注早期血脑屏障损伤,缩小梗死体积,促进神经功能恢复,其保护机制可能与米诺环素抑制脑组织明胶酶活性有关。

Objective To investigate the effects of minocycline on the disruption of the blood-brain barrier following transient focal cerebral ischemia in rats. Methods 28 Wistar rats were randomly divided into 4 groups ： the sham-operated group,the cerebral ischemia-reperfusion group,the minocycline group and the saline group. A series of MRI images were obtained to examine the infarct size and the BBB disruption. All rats received neurological evaluation before sacrifice. Brain MMP-2 and MMP-9 activities were defined by gelatin zymography. Results After 3.5 and 24h of reperfusion the lesion volumes on DWI and T2WI in the minocycline group were significantly smaller than those of the ischemia-reperfusion group and the saline group（P〈0. 05）. Similarly,the enhanced volume and signal intensity on postcontrast T：WI were also significantly lower in the minocycline group （P〈0. 05）. Minocycline improved neurological outcome and decreased activity of MMP-2 and MMP-9 after 24 hours of reperfusion （P〈0. 05）. Conclusion Minocycline attenuates BBB disruption, reduces infarct volume and improves neurological outcome after transient focal cerebral ischemia. The inhibition of gelatinases may be responsible for the protective effects of minocycline.