凝血酶对血脑屏障通透性影响的实验研究

目的　探讨凝血酶 (thrombin,TM)对血脑屏障 (blood brain barrier,BBB)通透性的影响及其可能机制。方法　 5 4只 SD大鼠随机分为 A、B、C 3组。 A组在右侧基底节立体定向注入 TM;B组注入 TM+组织蛋白酶 G(Cathepsin G,CATG) ;C组注入生理盐水。A、B组又随机分为注入后 6 h、2 4 h、4 8h、72 h亚组 ,应用干湿重法测定脑水含量 ,应用 Evans- blue测定 BBB通透性。结果　 TM脑内注射后 6 h同基底节区 BBB通透性明显增加 (P<0 .0 5 ) ,2 4 h时达高峰 (P<0 .0 1) ,持续至 4 8h(P<0 .0 5 ) ,然后逐渐消退 ,脑水含量的变化规律与 BBB通透性的变化类似。TM+CATG组在各个时间点 BBB通透性和脑水含量与对照组比较均无明显差异 (P>0 .0 5 )。结论　 TM增加 BBB通透性是其诱发脑水肿形成的主要机制。 TM对 BBB通透性的影响可能是通过激活蛋白酶激活受体 - 1(protease activated receptor- 1,PAR- 1)实现的

Effect of thrombin on the permeability of blood brain barrier

Objective To explore the effect of thrombin on the permeability of blood brain barrier (BBB) and its possible mechanism.Methods 54 Sprague Dawley rats were randomly divided into A,B,C groups. Thrombin, thrombin+cathepsin G or physiological saline were stereotaxically injected into right caudate nucleus in rats of A,B,C groups respectively.A and B groups included 6h,24h,48h and 72h subgroups after injection respectively.Rats were put to death at different time points.The permeability of BBB was measured by Evans Blue extravasion. Brain water content was determined by dry wet weight method.Results The permeability of BBB was increased at 6h after thrombin injection in ipsilateral caudate nucleus ( P <0.05),peaked at 24h( P <0.01),lasted until 48h( P <0.05) and then declined.The change pattern of brain water content was similar to that of BBB permeability .At all the time points,the permeability of BBB and brain water content after thrombin+cathepsin G injection had no significant difference compared with control group ( P >0.05).Conclusions The increased permeability of BBB may be one of the mechanisms of cerebral edema induced by thrombin. Effect of thrombin on the permeability may be due to activation of protease activated receptor 1(PAR 1).