半胱氨酸蛋白酶-3抑制剂z-DEVD-fmk对大鼠脑创伤后神经细胞凋亡及血浆血管内皮素、降钙素基因相关肽水平的影响  

The effects of caspase-3 inhibitor( z-DEVD-fmk ) on neuronal apoptosis and plasma levels of endothelium and calcitonin gene-related peptide in rats with traumatic brain injury

作　　者：官明[1] 陈礼刚 董劲虎[1] 胡迎春[1] 江涌[1] 黄昌仁[1] 

机构地区：[1]泸州医学院附属医院神经外科,646000

出　　处：《临床神经病学杂志》2014年第3期207-209,共3页Journal of Clinical Neurology

摘　　要：目的：探讨半胱氨酸蛋白酶（ caspase ）-3抑制剂z-DEVD-fmk对大鼠颅脑创伤后神经细胞凋亡及血浆血管内皮素（ ET）、降钙素基因相关肽（ CGRP）水平的影响。方法将24只SD大鼠随机分为正常对照组、创伤组、治疗组。每组8只。创伤组、治疗组制作改进的Feeney自由落体大鼠颅脑损伤模型。治疗组通过脑立体定位仪经脑室注射z-DEVD-fmk 10μl（1μg／μl ），创伤组仅注射生理盐水。用TUNEL法观察神经细胞凋亡情况，用放射免疫法检测ET、CGRP含量。结果创伤组和治疗组的血ET水平在创伤后24 h时达高峰，后逐步下降，创伤后各时间点均显著高于正常对照组（P＜0.05～0．01）。与正常对照组相比，创伤组和治疗组的血CGRP水平在创伤后24 h、48 h时明显降低（P＜0.05～0．01），后上升，72 h时差异无统计学意义。创伤组与治疗组相比的差异无统计学意义。根据免疫组化图像分析，正常对照组凋亡细胞率为（1．8±0．3）％，创伤组为（86．3±8．5）％，治疗组为（67．5±7．8）％。治疗组较创伤组神经细胞凋亡率减少，但与正常对照组相比凋亡率增加（ P＜0.05）。结论 z-DEVD-fmk能抑制创伤后神经细胞凋亡，与ET、CGRP变化没有相关性。Objective To study the effects of caspase-3 inhibitor （ z-DEVD-fmk） on neuronal apoptosis and plasma levels of endothelium （ ET ） , calcitonin gene-related peptide （ CGRP ） in rats with traumatic brain injury . Methods Twenty-two SD rats were randomly divided into normal control group ,traumatic group and therapy group , 8 rats per group.The traumatic and therapy group were made improved Feeney free-fall model;z-DEVD-fmk 10 μl （1μg/μl ） was injected into ventricles by Stereotaxic instrument in therapy group while normal saline was injected into in traumatic group .Neuronal apoptosis was detected by TUNEL staining;while ET and CGRP were detected by radioimmunoassay.Results ET in traumatic group and therapy group reached the peek at 24 h after intrauma,then dropped gradually , and were significantly higher than that in normal control group at each time point after intrauma （P〈0.05-0.01）.Compared with normal control group , CGRP in traumatic group and therapy group reduced at 24 h and 48 h after intrauma（P〈0.05-0.01）, then it rised, there was no satistically significant difference at 72 h. The difference was no satistically significance between traumatic group and therapy group . With the immunocytochemical method and image analysis , the rate of apoptosis in normal control group is （1.8 ±0.3）%, rate in traumatic group is （86.3 ±8.5）%, rate in theraphy group is （67.5 ±7.8）%.The rate of apoptosis in therapy group decreased significantly compared with traumatic group but increased dramatically compared with control group （ P〈0.05 ） .Conclusions z-DEVD-fmk can inhibit apoptosis of neurons after trauma .There is no significant correlation between z-DEVD-fmk and ET, CGRP.

关 键 词：脑创伤 凋亡 血管内皮素 降钙素基因相关肽 

分 类 号：R651.15[医药卫生—外科学]