摘要
目的探讨凝血酶(thrombin,TM)对血脑屏障(blood brain barrier,BBB)通透性的影响和细胞凋亡(Apoptosis)的可能机制。方法108只SD大鼠随机分为A、B、C3组,分别向大鼠右侧基底节区注入凝血酶、凝血酶加组织蛋白酶G(Cathepsin G,CATG)、生理盐水,于注射后6、24、48和72h取脑组织,测定BBB通透性(Evans-blue法)、脑水含量(干湿重法)以及Caspase-3蛋白表达(Western-blot)。结果TM脑内注射后6h同侧基底节区BBB通透性明显增加(P<0.05),24h时达高峰(P<0.01),持续至48h(P<0.05),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脑内注射后6h Caspase-3蛋白开始增加(P<0.01),24h达高峰(P<0.01),然后逐渐下降。TM+CATG组在各个时间点BBB通透性、脑水含量和Caspase-3蛋白表达与对照组比较均无明显差异(P>0.05)。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 recep-tor-1,PAR-1)实现的;凝血酶可能通过激活PAR-1受体诱导凋亡。
[Objective] To explore the effect and possible mechanism of thrombin on the permeability of blood brain barrier (BBB) and the brain cell apoptosis. [Methods] 108 Spragne-Dawley rats were randomly divided into A, B, C groups. Thrombin, th rombin+cathepsin G or physiological saline were stereotaxically injected into right caudate nucleus in rats of A, B, C group s respectively. Mter 6 h, 24 h, 48 h and 72 h, the brains were taken out to detect the permeability of BBB by Evans-blue extravasion and the water content of brain by dry-weight method or caspase-3 protein expression. [Results] The permeabihty of BBB was increased at 6 h after thrombin injection in ip-silateral caudate nucleus (P 〈0.05), peaked at 24 h (P 〈0.01), lasted until 48 h (P 〈0.05) and then declined. The change pattern of brain water content was similar to that of BBB permeability, caspase-3 protein expression was increased at 24 h after TM injection (P 〈0.05), peak at 48 h (P 〈0.01), and then declined. At all the time points, the permeability of BBB and brain water content or caspase-3 protein expression after thrombin+cathep-sin 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). TM may also induced apoptosis by PAR-1.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2007年第13期1565-1568,共4页
China Journal of Modern Medicine
基金
海南省自然科学基金(No.30215)
关键词
凝血酶
血脑屏障
脑水肿
凋亡
蛋白酶激活受体-1
thrombin
blood brain barrier
, cerebral edema
apoptosis
protease activated receptor-1