目的：半胱氨酸天冬氨酸酶(caspase)-1及其激活的细胞因子与许多疾病的炎症反应和凋亡有关,但与惊厥性脑损伤的关系目前尚不清楚。该研究旨在探讨caspase-1及其激活的细胞因子在发育期惊厥性脑损伤中的作用。方法：96只20日龄健康Sprague-Daw ley(SD)大鼠随机分为2组:对照组和惊厥组。通过三氟乙醚反复吸入制作发育期大鼠惊厥动物模型。RT-PCR方法检测各组动物反复惊厥后6 h,1,3,7 d大脑皮层caspase-1,IL-18,IL-1βmRNA的表达,同时观察脑含水量变化和光镜下大脑皮层神经元病理改变,并对脑损伤进行神经病理半定量积分。结果：①惊厥组各时间点大脑皮层caspase-1,IL-18 mRNA的表达均较对照组显著增高(P<0.05或<0.01);而IL-1βmRNA的表达呈双峰样改变,反复惊厥后6 h,1 d,7 d表达量较对照组显著增高(P<0.01),第3天表达量与对照组相比差异无显著性(P>0.05)。②惊厥后皮层神经元出现水肿和变性坏死,并可见炎性细胞浸润和凋亡细胞。③反复惊厥后6 h,1 d,3 d脑含水量均较对照组显著升高(P<0.01),第7天与对照组相比较差异无显著性(P>0.05);惊厥组各时间点脑损伤积分较对照组显著升高(P<0.01)。结论：caspase-1及其激活的细胞因子在发育期惊厥性脑损伤中发挥重要作用。

OBJECTIVE: The expressions of caspase-1 and cytokines activated by caspase-1 are associated with the pathophysiology of many diseases for its proinflammatory and proapototic peculiarity. However its relationship to brain injury of developing rats following recurrent seizures has not yet been identified. This study aimed to investigate the role of caspase1 and cytokines activated by caspase-1 in brain injury of developing rats following recurrent seizures. METHODS: A total of 96 postnatal 20 day Sprague-Dawley rats were randomly assigned into Control and Seizure groups.Seizures were induced in the Seizure group by flurothyl inhalation daily for six days. Brain tissues were sampled at 6 hrs, and at 1, 3, and 7 days after last seizure. The expressions of caspase-1, interleukin (IL) -18 and IL-1β mRNA in the cerebral cortex were detected by RT-PCR.The water content of the brain and the pathological changes of cortex nerve cells were observed. Brain injury was evaluated using a semiquantitative neuropathological scoring system. RESULTS: The levels of caspase-1and IL-18 mRNA in the cerebral cortex of the Seizure group were obviously higher than those in the Control group at 6 hrs, and at 1, 3, and 7 days after seizure (P<0.05 or P<0.01). The expression of IL-1β mRNA in the Seizure group exhibited a biphasic pattern: increased significantly at 6 hrs, and at 1 and 7 days post-seizure (P<0.01), but was not significantly different from the Control group at 3 days post-seizure. Edema, degeneration and necrosis of nerve cells in cerebral cortex, accompanying by inflammatory cell infiltration and apoptosis of nerve cells, were observed under a light microscope in the Seizure group after recurrent seizures. The water content of the brain in the Seizure group increased significantly compared with that in the Control group at 6 hrs, and at 1 and 3 days after recurrent seizures (P<0.01). The Seizure group had significantly higher neuropathological scores than the Control group at each time point (P<0.01). CONCLUSIONS: Caspase-1 and cytokines activated by caspase-1 play an important role in the developing brain injury after recurrent seizures.