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目的:探索促血管生成素-1(Ang-1)蛋白能否减少尿激酶溶栓的大鼠脑梗死模型出血转化率、出血量及其可能的机制。方法:清洁级SD大鼠按照随机分组法分为4组:假手术组,生理盐水对照组、尿激酶溶栓组、尿激酶+Ang-1组,每组24只。比较各组出血转化率、出血量、脑水肿、血脑屏障破坏情况和紧密连接蛋白occludin,ZO-1的表达。采用脑组织干湿重法评估脑水肿程度,伊文思蓝通透率评估血脑屏障破坏情况,RT-PCR和Western blot检测紧密连接蛋白occludin,ZO-1 mRNA的表达水平。结果:尿激酶溶栓组的出血量、脑水肿和血脑屏障破坏程度相较于其余各组明显增高(P<0.05);occludin,ZO-1的表达低于其余各组(P<0.05);尿激酶+Ang-1组的出血转化率、出血量、脑水肿和血脑屏障破坏程度低于尿激酶溶栓组(P<0.05)。Occludin,ZO-1表达比尿激酶溶栓组增高(P<0.05)。结论:Ang-1蛋白可减少尿激酶溶栓所致的脑出血、血脑屏障损失及脑水肿水平,其机制可能与增加紧密连接蛋白occludin,ZO-1的表达从而保护血脑屏障有关。
Objective: To investigate whether angiopoietin-1 (Ang-1) protein can reduce the hemorrhage rate and blood loss of cerebral infarction model induced by urokinase and its possible mechanism. Methods: Clean SD rats were randomly divided into 4 groups: sham operation group, saline control group, urokinase thrombolysis group and urokinase + Ang-1 group, 24 rats in each group. The hemorrhagic transformation rate, hemorrhage volume, cerebral edema, blood-brain barrier disruption and occludin, ZO-1 expression in each group were compared. The extent of brain edema was assessed by dry-wet method of brain tissue. The damage of blood-brain barrier was evaluated by Evan’s blue permeability. The expression of tight junction protein occludin and ZO-1 mRNA was detected by RT-PCR and Western blot. Results: The levels of hemorrhage, cerebral edema and blood-brain barrier in urokinase-thrombolytic group were significantly higher than those in other groups (P <0.05). The expression of occludin and ZO-1 were lower than those in other groups (P <0.05) The hemorrhage rate, hemorrhage volume, cerebral edema and blood-brain barrier disruption in urokinase + Ang-1 group were lower than those in urokinase thrombolysis group (P <0.05). Occludin, ZO-1 expression increased compared with urokinase thrombolysis group (P <0.05). CONCLUSION: Ang-1 can reduce cerebral hemorrhage, blood-brain barrier loss and cerebral edema induced by urokinase thrombolysis, which may be related to increasing the expression of tight junction proteins occludin and ZO-1 to protect the blood-brain barrier.