NSC23766对海马CA1区神经元缺血性损伤的保护机制  

Neuroprotective Mechanisms NSC23766 against Global Cerebral Ischemia in Rat Hippocampal CA1 Region

作　　者：韩东 武卿 蒋倩蓉 胡书群 许铁 

机构地区：[1]徐州医科大学救援医学研究所,江苏徐州221002 [2]徐州医科大学附属医院急救中心,江苏徐州221002

出　　处：《现代生物医学进展》2017年第35期6823-6827,共5页Progress in Modern Biomedicine

基　　金：江苏省自然科学基金面上研究项目(BK20161153);徐州医学院院长基金项目(2012KJZ16)

摘　　要：目的:探讨抑制Ras相关的C3肉毒素底物1(ras-related C3 botulinum toxin substrate 1,Rac1)活化对海马CA1区神经元缺血性损伤产生保护作用的机制。方法:采用大鼠大脑四动脉结扎建立全脑缺血模型,SD雄性大鼠按照随机数字法被分为假手术(Sham)组,缺血再灌注(ischemia/reperfusion,I/R)组,溶剂对照(Vehicle)组,NSC23766预处理(NSC)组。Vehicle组、NSC组分别在缺血前30 min侧脑室注射0.9%的生理盐水(5μL)和Rac1特异性抑制剂NSC23766(25μg溶于5μL 0.9%的生理盐水)。蛋白免疫印迹法检测海马CA1区c-Jun、活化转录因子-2(activating transcription factor2,ATF2)、P-c-Jun、P-ATF2蛋白含量的变化。焦油紫染色法观察海马CA1区神经元的存活情况。结果:再灌注1d时,与I/R组相比,NSC组P-c-Jun、P-ATF2蛋白含量明显降低(P<0.05);而c-Jun、ATF2蛋白含量没有明显变化;焦油紫结果显示,NSC组大鼠海马CA1区神经元死亡明显减少(P<0.05)。结论:NSC23766抑制Rac1活化对神经元缺血性损伤产生的保护作用可能与c-Jun、ATF2磷酸化水平降低有关。本研究的发现为临床治疗缺血性脑中风提供了新的靶点。Objective： To explore the neuroprotection mechanisms of Inhibit the activation of ras-related C3 botulinum toxin sub- strate 1 （Rac1） against global ischemia in rat Hippocampal CA1 Region. Methods： Using 4-vessel occlusion （4-VO） as brain ischemia model. The SD Male rats were randomly assigned into sham （sham） group, ischemia / repeffusion （I / R） group, Vehicle control group （Vehicle）, and NSC23766 Pretreatment （NSC） group using a random number table. Vehicle group and NSC group were respectively injected 0.9% saline （5 μL） and Rac1 specific inhibitor NSC23766 （25 ug for 5 μL 0.9% saline） by intracerebroventricular to the rats 30 min before ischemia. The levels of c-Jun, activating transcription factor2 （ATF2）, P-c-Jtm and P-ATF2 proteins in hippoeampal CA1 region were detected by Western Blot and Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Results： After 1 day of reperfusion, Compared with I / R group, the content of P-c-Jun and P-ATF2 protein in NSC group was significantly lower than that in I / R group （P〈0.05）, but the content of c-Jun and ATF2 protein was not significantly Changes. Cresyl violet staining showed that the neuronal death ofhippocampal CA1 regions of rats in the p38-I group was significantly decreased （P〈0.05）. Conclusion： Neuroprotective effect ofNSC23766 inhibited Rac1 activation against ischemic brain injury may be associated with a decrease in phosphorylation levels of c-Jun and ATF2 proteins. The findings of this study provide a new target for clinical treatment of ischemic stroke.

关 键 词：缺血再灌注 RACL NSC23766 C-JUN ATF2 

分 类 号：R-33[医药卫生] R743.31