脑脉通联合溶栓对血栓栓塞性脑缺血大鼠纤溶酶原激活物及其受体的影响

Effects of NaoMaiTong combined with thrombolysis on activator of plasminogen and its receptor in rats with thrombus-occluded cerebral ischemia

脑缺血损伤可引起血脑屏障破坏,溶栓治疗可以再通血流,保护脑组织免受损伤,但可使颅内出血增加。脑脉通已被证实对脑缺血损伤有保护作用。本实验拟对脑脉通联合溶栓对脑缺血大鼠血脑屏障的保护作用及其可能的作用机制进行探讨。将实验大鼠随机分组;运用自体血栓结合线栓阻塞大鼠大脑中动脉制备血栓栓塞性脑缺血动物模型;大鼠缺血后3h、6h、9h经导管由区域动脉进行溶栓;动脉给药后24h观察大鼠脑组织颅内出血率变化,用免疫组织化学法测定脑组织IgG、IV型胶原蛋白(CoLIV)、尿激酶型纤维蛋白酶原激活物(uPA)和uPA受体(uPAR)表达的变化。结果显示,模型组大鼠脑内出血率增高,其9h、6h组IgG水平增高、CoLIV降低,各组uPA和uPAR表达明显;溶栓组颅内出血率较模型组增高,各用药组9h的IgG降低、Co-LIV增强,uPA和uPAR表达减弱;各组9h较3h和6h的IgG表达增强,CoLIV减弱,uPA和uPAR表达显著;联合组的颅内出血率较溶栓组降低,其9h组的IgG分别较脑脉通组降低、CoLIV增强,uPA和uPAR表达减弱。上述结果提示,脑缺血可引起血脑屏障破坏,溶栓可增加颅内出血率,脑脉通联合溶栓可保护血脑屏障受损,降低颅内出血的发生,其作用可能与降低脑组织uPA和uPAR表达以增加CoLIV水平有关。

Cerebral ischemia could lead to the injury of brain blood barrier （BBB）. Therapy of thrombolysis could make the brain blood flow again and protect brain tissue against injury. Thrombolysis could also result in the increase of intracranial hemorrhage （ICH）. The effect of NaoMaiTong on cerebral ischemia injury has been confirmed. In this study, the protective effects of NaoMaiTong combined with UK thrombolysis on BBB in rats with thrombus-occluded cerebral ischemia would be discussed and then to explore the possible mechanism. Rats were randomly divided into different groups. Thrombus-occluded cerebral ischemia model group was duplicated using autologous blood blot and inserted nylon thread. Rats were administrated with thrombolysis therapy through artery at 3, 6, and 9 h after cererbral ischemia. At 24 h of administration through artery, intracalvarium hemorrhage ratio （IHR） of rats was observed, and the expression of IgG, CoLIV uPA and uPAR were measured. The results showed that rats IHR increased in model group, and the levels of IgG in 9 h and 6 h model group increased, while the level of CoLIV decreased, and brain uPA and uPAR expressed significantly. IHR in thrombolysis group was higher than that in model group. In each 9 h administration group, IgG was lower, while CoLIV was higher, and the expression of uPA and uPAR weakened. The expression of IgG , uPA and uPAR all enhanced in 3 h and 6 h in comparison with that in 9 h, while the expression of CoLIV weakened. IHR in combination group decreased than that in thrombolysis group, and the levels of IgG, uPA and uPAR were all lower in comparison with NaoMaiTong group, while the expression of CoLIV increased. The present results suggest that damage of BBB could be caused by injury of cerebral ischemia, and thrombolysis therapy make II-IR increased. NaoMaiTong combined with thrombolysis could decrease IHR and protect BBB from impairment, and the effects are thought to be related to the decrease of the expression of brain uPA and uPAR and then to increase the level of CoLIV.