17β-雌二醇通过PI3K-Akt信号通路抑制丙泊酚诱导皮层神经元凋亡  

17β-estradiol protects cortical neurons from propofol-induced apoptosis by activating PI3K-Akt signaling pathway

作　　者：李建立[1] 庞鑫鑫[2] 郭洪霞[1] 王晓宇[1] 吴红海[2] 侯艳宁[2] 

机构地区：[1]河北省人民医院麻醉科,河北石家庄050051 [2]白求恩国际和平医院药剂科,河北石家庄050082

出　　处：《中国病理生理杂志》2016年第1期58-63,共6页Chinese Journal of Pathophysiology

基　　金：河北省卫生厅指令性课题(No.ZL20140095)

摘　　要：目的:探讨17β-雌二醇对丙泊酚诱导原代培养皮层神经元凋亡的影响及机制。方法:原代培养7d的大鼠皮层神经元,给予不同浓度丙泊酚和或17β-雌二醇处理12 h,用MTT法检测神经元存活率变化,Hoechst33258核染色法检测神经元调亡,Western blot法测定神经元p-Akt蛋白的变化。结果:与溶剂对照组比较,丙泊酚呈剂量依赖性降低神经元存活率(P<0.05);与丙泊酚组比较,17β-雌二醇呈剂量依赖性提高神经元存活率(P<0.05),PI3K/Akt激动剂IGF组神经元存活率显著增加(P<0.01)。与溶剂对照组比较,丙泊酚组神经元凋亡率显著增加(P<0.01),丙泊酚+17β-雌二醇组神经元凋亡率较丙泊酚组显著下降(P<0.01),LY294002预处理可阻断17β-雌二醇的作用,使细胞凋亡率增加(P<0.01)。与溶剂对照组比较,丙泊酚呈剂量依赖性降低神经元p-Akt蛋白水平(P<0.05);与丙泊酚组比较,17β-雌二醇呈剂量依赖性提高神经元p-Akt蛋白水平(P<0.05);与丙泊酚+17β-雌二醇组比较,LY294002预处理组p-Akt蛋白水平显著下降(P<0.01)。结论:17β-雌二醇可抑制丙泊酚诱导的原代培养皮层神经元凋亡,其机制可能与激活PI3K-Akt信号通路有关。AIM： To investigate the protective effects and the mechanisms of 17β-estradiol on the propofol-induced neuroapoptosis in primary cultured cortical neurons. METHODS： The neurons were cultured for 7 d and treated with different concentrations of propofol and / or 17β-estradiol,respectively. The neuron viability,neuroapoptosis and the protein level of p-Akt was determined by MTT assay,Hoechst 33258 staining and Western blot 12 h after different treatments,respectively. RESULTS： Compared with vehicle-control group,propfol inhibited neuron viability in a dose-dependent manner（ P 0. 05）. Compared with propofol treatment group,17β-estradiol increased the neuron viability in a dose-dependent manner（ P 0. 05）,and IGF increased the neuron viability greatly（ P 0. 01）. Compared with vehiclecontrol group,the number of apoptotic neurons which was significantly decreased by treatment of 17β-estradiol was markedly increased by propofol（ P 0. 01）. Compared with the 17β-estradiol ＋ propofol group,LY294002 increased the number of apoptotic neurons（ P 0. 01）. Compared with vehicle-control group,propfol decreased the protein level of p-Akt in a dose-dependent manner（ P 0. 05）. Compared with propofol treatment group,17β-estradiol increased the protein level of p-Akt in a dose-dependent manner（ P 0. 05）. Compared with 17β-estradiol ＋ propofol group,LY294002 significantly decreased the protein level of p-Akt（ P 0. 01）. CONCLUSION： 17β-estradiol exerts the neuroprotective effects against propofol-induced neuroapoptosis by activating the PI3K-Akt signaling pathway.

关 键 词：丙泊酚 17Β-雌二醇 皮层神经元 细胞凋亡 PI3K-AKT信号通路 

分 类 号：R363[医药卫生—病理学]