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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 observe the effect of doxycycline on the permeability of blood-brain barrier of urokinase-thrombolytic rats at different time points after cerebral ischemia, and to evaluate its intervention effect on hemorrhagic transformation after thrombolysis. Methods The rat model of middle cerebral artery occlusion (MCAO) was used to determine the expression of MMP-9, the permeability of the blood-brain barrier, the amount of cerebral hemorrhage and the incidence of hemorrhage. Results Urokinase thrombolytic therapy at each time point increased the expression of MMP-9, the permeability of the blood-brain barrier, the amount of cerebral hemorrhage and the incidence of hemorrhage increased compared with the control group, and the later the thrombolytic time, the more obvious the increase; the combination of doxycycline and urine Compared with the corresponding time point urokinase thrombolysis group, the expression level of MMP-9 and the permeability of the blood-brain barrier were significantly decreased, while the incidences of cerebral hemorrhage and hemorrhage were both decreased. Conclusion Doxycycline combined with urokinase thrombolytic therapy can reduce the expression of MMP-9 after thrombolysis in rats with focal cerebral ischemia and relieve the intracranial hemorrhagic transformation caused by the destruction of blood-brain barrier after urokinase thrombolysis at different time points.