活化的GABAB受体通过抑制P38/ATF2信号通路减轻缺血性海马CA1区神经元凋亡的研究  

Activation of GABA_B receptors attenuates neuronal apoptosis through inhibiting P38/ATF2 pathway after cerebral ischemia and reperfusion

作　　者：韩东 蒋倩蓉 张薇 武卿 胡书群 许铁 HAN Dong;JIANG Qian—rng;ZHANG wei;WU Qing;HU Shun—qun;XU Tie(Institute Emergency Rescue Medicine,Xuzhou Medical University,Xuzhou 221002,China)

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

出　　处：《中国急救复苏与灾害医学杂志》2017年第11期1062-1065,共4页China Journal of Emergency Resuscitation and Disaster Medicine

摘　　要：目的探讨活化的γ-氨基丁酸B(GABAB)受体对缺血性海马CA1区神经元产生的保护作用是否与调节P38/活化转录因子2(ATF2)信号通路有关。方法采用四动脉结扎全脑缺血模型。SD雄性大鼠随机分为假手术组(Sham)、缺血/再灌注组(I/R)、溶剂对照组(Saline)、GABAB受体激动剂氯苯氨丁酸预处理组(Bac)。Saline组、Bac组于全脑缺血前30min分别经腹腔注射0.9%生理盐水和20mg/kg氯苯氨丁酸。运用蛋白免疫印迹法检测大鼠海马CA1区P38、p-P38、ATF2与p-ATF2含量的变化。结果再灌注1d时,Bac组P—P38、p-ATF2水平明显低于I/R组;差异均有统计学意义(P〈0.05)。而p38、ATF2蛋白含量没有明显变化。结论GABAB受体的活化对缺血性海马CA1区神经元产生保护的机制可能部分通过降低P38及ATF2的磷酸化水平来实现的。Objective To investigate whether the protective effect of activated"y-amino butyric acid B{GABA(B)}receptors on ischemic hippocampal CA1 region neurons is related to the regulation of P38/Activating Transcription Factor 2(ATF2)signaling pathway.Methods Four-artery ligation of global cerebral ischemia model was used.SD rats were randomly divided into:sham group,ischemia/reperfusion group(I/R),vehicle control group(Vehicle),GABA(B)receptor agonist Baclofen,pretreatment group(Bac).Vehicle group and Bac group were injected intraperitoneally with 0.9%Saline or Baclofen(20 mg/kg)30 minutes(min)before the cerebra ischemia,respectively.The changes of P38,p-P38,ATF2 and p-ATF2 protein in hippocampal CA1 region were detected by immunoblotting.Results The levels of p-P38 and p-ATF2 in Bac group were significantly lower than those in I/R group;The differences between I/R group and Bac were statistically significant(P〈0.05).But the content of Bcl-2 and Bax protein shew no significant difference.Conclusion The mechanism of GABA(B)receptor activation to protect neurons in ischemic hippocampal CA1 region may be achieved by reducing the phosphorylation of P38 and ATF2 in part.

关 键 词：氯苯氨丁酸 海马 神经元 缺血/再灌注 

分 类 号：R743.31[医药卫生—神经病学与精神病学]