Caspase-1抑制剂对大鼠外伤性脑损伤后脑水肿、神经细胞凋亡和IL-18表达的影响

目的研究天冬氮酸特异性半胱氨酸蛋白酶-1（Caspase-1）抑制剂对大鼠脑损伤后脑水肿、细胞凋亡和IL-18表达的影响。方法雄性sD大鼠170只，随机分为正常组、损伤组、治疗组。用改良的Feeney方法制备损伤模型。治疗组分别于损伤前后30min经右侧脑室注射Caspase-1抑制剂——z-YVAD—fmk。损伤组与治疗组分别于脑损伤后6、24、72、168h点断头取脑。检测脑组织含水量、Caspase-1与IL-18表达及细胞凋亡。结果伤后6、24、72及168h，损伤组脑损伤周围皮质组织含水量、Caspase-1与IL—18的表达及细胞凋亡较正常组明显增多（P〈0．05），但伤后6、24及72h，治疗组脑损伤周围皮质组织含水量、Caspase—1与IL-18的表达及细胞凋亡虽明显高于正常组，但与损伤组相比则明显降低（P〈0．05）。结论Caspase-1及其激活的细胞因子IL—18在创伤性脑损伤后脑水肿和细胞凋亡中起重要作用，Caspase-1抑制剂对脑创伤后神经细胞损害具有保护作用。

Effect of Caspase-1 Inhibitor, Z-Yvad-Fmk on IL-18 Expression and Neuron Apoptosis and Cerebral Eden after Traumatic Brain Injury in Rats

Objective To investigate the effect of caspase-1 inhibitor, z-YVAD-fmk on brain edema, neuron apoptosis and interlenkin-18 （IL-18） expression following traumatic brain injury in rats. Methods One hundred and seventy male SD rats were randomly divided into normal group （10 rats）, injury group 80 rats and therapy group （80 rats）. The traumatic brain injury model in rats was prepared by modified Feeney method. The animals in therapy group received injection of z-YVAD-fmk into the right lateral ventricles 30 minutes before and after the injury. Twenty rats in both the injury and therapy groups were decapitated 6, 24, 72 and 68 hours respectively after the injury. The water content, the expressions of Caspase-1 and IL-18, and neuron apoptosis in the cerebra｜ tissues were determined. Results The water content of the cerebral tissues was significantly higher in the injury group than that in the therapy group 6, 24, 72 and 168 hours after the injury （P〈0.05）. The positive cell rate of neuron apoptosis and the levels of Caspase-1 and IL-18 expression in the cerebral tissues were significantly higher in the injury group than those in the therapy group 6, 24 and 72 hours after the injury （P〈0.05）. Conclusions Caspase-1 and IL-18 activated by it may play an important role in the brain edema and neuron apoptosis induced by brain injury. Caspase-1 inhibitor can alleviate cerebral injury secondary to brain trauma.