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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 investigate the effect of thrombin on the permeability of blood brain barrier (BBB) and the possible mechanism of Apoptosis. Methods 108 Sprague-Dawley rats were randomly divided into A, B and C3 groups. Thrombin, cathepsin G (CATG) and normal saline were injected into the right basal ganglia of rats, The brain tissues were harvested at 24, 48 and 72 hours. The BBB permeability (Evans-blue method), brain water content (dry and wet weight) and Caspase-3 protein expression (Western-blot) were measured. Results The permeability of BBB in the ipsilateral basal ganglia increased significantly (P <0.05) at 6h after intracerebral injection of TM and peaked at 24h (P <0.01), and continued to 48h (P <0.05) The variation of BBB permeability is similar to that of BBB. Six hours after TM injection, Caspase-3 protein began to increase (P <0.01), peaked at 24h (P <0.01), and then gradually decreased. The BBB permeability, brain water content and Caspase-3 protein expression in TM + CATG group were not significantly different from those in control group at all time points (P> 0.05). Conclusion TM increases BBB permeability is the main mechanism of inducing cerebral edema. The effect of TM on BBB permeability may be through the activation of protease activated receptor-1 (PAR-1); thrombin may induce apoptosis through activation of PAR-1 receptor.