强力霉素对溶栓脑缺血大鼠血脑屏障通透性的影响

Influence of doxycycline on the permeability of the brain-blood barrier after urokinase thrombolysis in rats

目的观察强力霉素对脑缺血不同时间尿激酶溶栓大鼠血脑屏障通透性的影响,评价其对溶栓后出血性转化的干预效果。方法采用大鼠自体血栓塞大脑中动脉闭塞(MCAO)模型,分别测定MMP-9表达水平、血脑屏障通透性、脑出血量和出血发生率。结果各时间点尿激酶溶栓治疗使MMP-9表达增加,血脑屏障通透性、脑出血量和出血发生率较对照组增加,且溶栓时间越晚增加越明显;强力霉素联合尿激酶溶栓组与相应时间点尿激酶溶栓组比较MMP-9表达水平和血脑屏障通透性显著降低,而脑出血量和出血发生率均有下降趋势。结论强力霉素联合尿激酶溶栓治疗可降低脑缺血大鼠溶栓后MMP-9高表达,减轻不同时间点尿激酶溶栓后血脑屏障破坏导致的颅内出血性转化。

Objective To study the influnence rier after urokinase thrombolysis therapy at different of doxycycline on the permeability ot the bram-Dlood oartime in rats with thrombusoccluded cerebral ischemia, and to evaluae the effect of doxycyeline on the cerebral hemorrhagic transformation after urokinase thrombolysis therapy. Methods A focal cerebral iscbemia of rats were established by embolizing left middle cerebral artery with autologous blood clots. The expression of MMP-9 was detected with inmmunohistochemical staining, the permeability of the brain-blood barrier was observed with Evan＇s blue, the rate of cerebral hemorrhage and the cerebral hemorrhage content were quantified with spectrophotometer assay. Results There were increased MMP-9 expression, the permeability of the brain-blood barrier and the cerebral hemorrhage content with urokinose treatment. And there were obviously increased more than 6 hours after ischemic stroke. Doxycycline combined with urokinase thrombolysis therapy decreased MMP-9 expression, the permeability of the brain-blood barrier,the cerebral hemorrhage content and the rate of hemorrhage. Conclusions Doxycycline combined with urokinase attenuates the permeability of the brain blood barrier,and reduces inducing hemorrhagic transformation after urokinase thrombolysis therapy at different time in rats with ischemie stroke model.