盐酸戊乙奎醚对新生大鼠缺氧缺血性脑病模型脑细胞钙离子浓度及天冬氨酸特异性半胱氨酸蛋白酶-3表达的影响  

The effects of Penehyclidine Hydrochioride on [Ca2＋]i and the expression of cysteine-containing aspartare-specific proteases-3 in neural cells of neonatal rats with hypoxic-ischemic encephalopathy

作　　者：李立[1] 李瑞兰[1] 邢莉[1] 李海永[1] 李宏向[1] 杨明峰[2] 

机构地区：[1]济南市第四人民医院新生儿科,250031 [2]泰山医学院生命科学研究所,泰安271000

出　　处：《中国小儿急救医学》2012年第1期71-75,共5页Chinese Pediatric Emergency Medicine

摘　　要：目的探讨盐酸戊乙奎醚（长托宁）对新生大鼠缺氧缺血性脑病（hypoxic-ischemic en-cephalopathy，HIE）模型脑细胞内钙离子浓度[Ca2＋]；及天冬氨酸特异性半胱氨酸蛋白酶-3（cysteinecontaining aspartate—specific proteases-3，Caspase-3）表达的影响。方法新生7日龄健康SD大鼠，共128只，随机分为4组：假手术对照组（Sham组，n=32），HIE模型组（HIE组，n=32），尼莫地平干预组（N组，n=32）及长托宁干预组（P组，n=32）。各组于手术后不同时间点（2h，4h，6h，12h）分批采集脑组织标本。用共聚焦激光显微镜和荧光显微镜分别观察不同组及各组不同时间点大鼠脑皮层细胞[Ca2＋]；和Caspase-3的表达。结果HIE组大鼠脑皮层细胞[Ca2＋]，和Caspase-3的表达，显著高于Sham组（P〈0．01），缺氧缺血后2h，[Ca2＋]i和Caspase-3表达即增加，随着时间延长，[Ca2＋]，和Caspase-3表达逐渐增加，12h时显著高于其他时间点（P〈0．05）。N组与P组的[Ca2＋]；和Caspase-3表达较HIE组明显降低（P〈0．01），但仍高于Sham组（P〈0．01）。N组与P组之间[Ca2＋]；和Caspase-3表达差异无统计学意义（P〉0．05）。N组与P组内12h时[Ca2＋]j和Caspase-3表达与6h比较，差异无统计学意义（P〉0．05）。结论长托宁可显著缓解缺氧缺血后脑皮层细胞钙超载并减少Caspase-3表达，进而减少脑细胞死亡，起到保护脑细胞的作用。Objective To explore the influences of Penehyclidine Hydrochloride on [ Ca2＋ ] i and the expression of cysteine-containing aspartate-specific proteases-3 （ Caspase-3 ） in neural cells of neonatal rats after hypoxic-ischemic injury within 12 h. Methods Seven-day-old Sprage-Dowley rats （n = 128） were randomly assigned into four groups：Sham group （sham operation group, n = 32）, hypoxic-ischemic encephalopathy （HIE） group （ HIE models, n = 32 ）, N group （ HIE models treated with Nimodipine, n = 32 ）, and P group （HIE models treated with Penehyclidine Hydrocloride, n = 32）. Brain tissues were collected at different time points （2 h,4 h,6 h,and 12 h） after modeling. We utilized fluorescent microscope to detect the expres- sion of Caspase-3 via making frozen slices of rat brain tissue, while [ Ca2＋ ] i of neural cells in live brain slices of rats was measured by laser scanning confocal microscope. Results Compared with Sham group, both [ Ca2 ＋ ] i and the expression of Caspase-3 of neural cells increased significantly （ P 〈 0. 01 ） in brain cortex in HIE group. [ Ca2＋] i and Caspase-3 activity increased gradually with time since 2 h after making HIE models and reached a peak at the time points of 12 h （ P 〈 0. 05 ）. In N group and P group, both of [ Ca2＋ ]i and Caspase-3 decreased compared with HIE group （P 〈 0.01 ） ,however,there was no significant difference be- tween N group and P group （ P 〉 0. 05 ）. In addition, [ Ca2＋ ] i and Caspase-3 activity had no significant difference between 6 h and 12 h （P 〉 0. 05 ）. Conclusion Penehyclidine Hydroclofide can protect the brain tissue from hypoxic-ischemic injury via relief of calcium overload and inhibition of Caspase-3 activity.

关 键 词：长托宁 缺氧缺血性脑病 钙 天冬氨酸特异性半胱氨酸蛋白酶-3 大鼠 新生 

分 类 号：R722.1[医药卫生—儿科]