Caspase-3抑制剂z-DEVD-fmk对大鼠——脑损伤的保护作用  

Role of caspase-3 inhibitor z-DEVD-fmk in protecting rat traumatic brain injury

作　　者：杨小锋[1] 刘伟国[1] 陈景森[1] 黄欣[1] 沈宏[1] 吕世亭[1] 

机构地区：[1]浙江大学医学院附属第二医院神经外科,杭州310009

出　　处：《中华创伤杂志》2006年第11期848-851,共4页Chinese Journal of Trauma

基　　金：浙江省医药卫生科学研究基金(2002A046)

摘　　要：目的研究caspase-3抑制剂z-DEVD-fmk对大鼠外伤性脑损伤(traumatic brain iniury,TBI)后神经细胞凋亡、脑含水量影响。方法分为假手术组、等渗盐水组、抑制剂组,采用改良的Feeney自由落体损伤模型,于损伤前后各30 min右侧脑室注射z-DEVD-fmk或等渗盐水,72 h后,断头取脑,用HE染色及电镜观察形态学变化,用干湿法测量脑含水量,流式细胞(An- nexin-V/PIFCM)及末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷三磷酸缺口末端标记(TUNEL)法检测神经细胞凋亡。结果在外伤中心区可见大量神经细胞坏死；损伤周围区神经细胞数量减少,出现细胞凋亡的特征,少量细胞出现坏死,等渗盐水组相对于抑制剂组较为明显；假手术组以正常细胞为主。抑制剂组大鼠损伤周围脑组织凋亡细胞数及脑含水量明显高于假手术组；但较等渗盐水组明显减少。结论大鼠脑损伤后在损伤周围区存在大量神经细胞凋亡；使用z- DEVD-fmk抑制caspase-3活性以后,能减少凋亡、减轻脑水肿,起到脑保护作用。Objective To investigate the protective effect of caspase - 3 inhibitor z - DEVD - fmk on neurocyte apoptosis and brain water content after traumatic brain injury in rats. Methods Rats were divided into sham operation group, isotonic saline solution group and capase -3 inhibitor group. Rat traumatic brain injury mode was made by modified Feeney free dropping objective and injected with z - DEVD -fmk or isotonic saline solution into the right lateral ventricle 30 minutes before and after injury. At 72 hours after injury, all rats were decapitated to investigate the brain morphological change with HE stain and electron microscopy, The water content was calculated by dry and wet method, And the neurocyte apoptosis was detected by TUNEL and flow cytometry （FCM）. Results Lots of neurocytes appeared as apoptotic changes around injury area, But there was less apoptotic neurocytes in the isotonic saline solution group than those in the capase - 3 inhibitor group, Normal neurocytes were mostly founded in the sham operation group. Apoptotic neurocytes and water content around injury area in the capase -3 inhibitor group were higher than those in the isotonic saline solution group. While the number of apoptotic neurocytes and water content decreased obviously in the capase- 3 inhibitor group. Conclusion Apoptosis exists in rat brain after acute brain injury. Caspase - 3 inhibitor of z - DEVD - fmk shows a neuroprotective effect by decreasing apoptosis and brain water content.

关 键 词：脑损伤 CASPASE类 半胱氨酸酶抑制剂 凋亡 神经元 

分 类 号：R651.15[医药卫生—外科学]