脑室注射N-苯甲基氧化碳酰-缬氨酸-丙氨酸-天冬氨酸-氯化丙酮对新生鼠缺氧缺血性脑损伤的保护作用  

Protective Effect of Caspase Inhibitor on Neonatal Rat with Hypoxia-Ischemia Brain Damage

作　　者：柴斌英[1] 刘家浩[1] 

机构地区：[1]东南大学附属中大医院儿科,南京210009

出　　处：《实用儿科临床杂志》2006年第2期75-77,共3页Journal of Applied Clinical Pediatrics

基　　金：东南大学博士人才启动基金项目资助(492-2003YJ15)

摘　　要：目的研究广谱Caspase抑制剂N-苯甲基氧化碳酰-缬氨酸-丙氨酸-天冬氨酸-氯化丙酮(zVAD-fmk)对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用。方法将新生7日龄SD大鼠36只随机分为缺氧缺血(HI)对照组(A)、zVAD-fmk治疗组(B)和假手术组(C)。B组动物于HI前即刻脑室注射zVAD-fmk 1μg,A组注射同体积PBS。建立HIBD动物模型,观察HIBD模型大鼠HI后24 h脑含水量及流式细胞术检测海马细胞凋亡百分率1、4 d体质量增长率和脑组织病理变化。结果HI后24 h,B组HIBD新生鼠结扎侧脑组织含水量、海马神经细胞凋亡率较A组明显减少;HI后14 d体质量增长率B组与A组无显著差异;缺血侧皮质、海马神经元死亡率B组较A组明显降低。结论脑室注射zVAD-fmk可减少HIBD后早期和中期神经细胞凋亡,对新生大鼠HIBD具有一定保护作用。Objective To observe the protection of Caspase inhibitor （zVAD- fmk, benzyloxycarbonyl Val- Ala- Asp - fluoromethyl ketone） on neonatal rats with hypoxic- ischernic brain damage（HIBD）. Methods Thirty - six neonatal rats, 7 days old, were randomly divided into hypoxic- ischemic（HI） control group（A） ,zVAD- fmk treated group（B） and sham group（C）. Before HI insult, a pan- Caspase inhihitor, zVAD - fmk or normal buffer solution was injected into the cerebral ventricle. The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer（Annexin V/PI） at 24 hours after HI insult. The effect on body weights （percentage of increased weight,WIP） and macroscopical changes（percentage of cortox and hippocampal dead neurons） were assessed at 14 days. Results Compared with group A, the water content of ischemic hernisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly. The difference of percentage of increased weight at 14 days in group B was not significantly. Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A. Conclusion Intracerebral administration of zVA13 - fmk has protective effects on hypoxic- ischemic brain damage in neonatal rats.

关 键 词：脑缺氧 脑缺血 CASPASE抑制剂 凋亡 大鼠 

分 类 号：R722.12[医药卫生—儿科]