阿加曲班对大鼠脑出血后血肿周围基质金属蛋白酶2表达的影响

Effect of argatroban on the expression of matrix metalloproteinase-2 in perihematomal tissue after intracerebral hemorrhage in rats

目的探讨阿加曲班对大鼠脑出血后血肿周围组织基质金属蛋白酶2(MMP-2)表达的影响。方法采用自体血注入法建立大鼠脑出血模型,于脑出血后3h,颅内原位注入阿加曲班(0.5μg/ml)。分别用Westernblot和免疫组化方法检测血肿周围组织MMP-2的表达,伊文思蓝(EB)测血脑屏障(BBB)通透性,干湿重法测脑组织含水量,并与假手术组相比较。结果在脑出血后24h,同侧基底核MMP-2的表达至高峰,脑出血组、等渗盐水组和阿加曲班干预组的MMP-2阳性细胞数分别为21.8±0.9、3.2±0.4和14.9±1.0;EB含量分别为(20.8±0.9)、(4.6±0.7)和(15.4±0.9)ng/mg;脑组织含水量分别为(84.3±1.1)、(78.7±1.5)和(81.2±1.6)%。脑出血组与等渗盐水组及阿加曲班干预组同侧基底核的MMP-2表达、EB含量和脑组织含水量比较,差异均有统计学意义(P<0.01,P<0.05)。结论凝血酶可能通过促进MMP-2的表达,诱导脑出血后脑水肿的形成,阿加曲班能明显减轻大鼠脑出血后血-脑屏障损伤和血肿周围脑组织的水肿。

Objective To investigate the effect of argatroban on the expression of matrix metalloproteinase-2(MMP-2)in perihematomal tissue after intracerebral hemorrhage(ICH)in rats.Methods A rat model of ICH was induced by autologous blood injection.In situ injection of argatroban(0.5 μg/mL)into hematoma was performed 3 hours after ICH.Then the expression of MMP-2 in perihematomal tissue was detected by Western blot and immunohistochemistry,respectively;the permeability of blood-brain barrier(BBB)was assessed by Evan...