【摘要】 目的观察丙泊酚对全脑缺血大鼠海马CA1区谷氨酸转运体1(GLT-1)表达的影响。方法采用四血管闭塞法建立全脑缺血模型;脑缺血前3 h静脉输注丙泊酚90 mg·kg-1,首次剂量(总剂量的1/3)15 min内推注,剩余剂量持续输注1 h。脑缺血再灌注后于0,12,24,48 h和7 d取材。光镜下观察海马CA1区的组织学分级和神经元密度,Western印迹法检测海马CA1区GLT-1的表达。结果组织学分级结果显示,假手术组及丙泊酚对照组所有动物均为0级,脑缺血模型组有5只动物均为Ⅲ级。丙泊酚+脑缺血组中3只动物的组织学分级为0级,2只动物为Ⅰ级。假手术组及丙泊酚对照组神经元密度分别为185±12及(181±11)mm-1。模型组中锥体细胞几乎全部死亡。与脑缺血组相比,丙泊酚+脑缺血组神经元密度为(125±14)mm-1,说明存活细胞数显著增高(P<0.05)。Western印迹结果显示,与同一时间点的假手术组相比,脑缺血后12 h,GLT-1的表达显著增强(0.31±0.03 vs 0.38±0.04),随后逐渐降低,在脑缺血后7 d显著低于假手术组(0.19±0.03 vs 0.29±0.04)。丙泊酚对照组GLT-1的表达保持在较高的水平(0.47±0.05),直到7 d才降至假手术组水平0.29±0.03。在再灌注后24和48 h时,丙泊酚明显逆转脑缺血造成的GLT-1表达的下降,GLT-1表达分别为0.45±0.04 vs 0.29±0.04和0.47±0.05 vs 0.27±0.04(P<0.05),在7 d时与假手术组相当。结论丙泊酚可保护海马CA1区的锥体细胞抵御缺血打击,并上调了大鼠海马CA1区GLT-1的表达。更多还原

【Abstract】 OBJECTIVE To observe the effect of propofol on glutamate transporter-1(GLT-1) expression of the CA1 hippocampus by Western blotting analysis in global brain ischemic rat.METHODS A rat global cerebral ischemic model was established by four-vessel occlusion.Propofol 90 mg·kg-1 was infused via veins at 3 h before brain ischemia.The initial dose(1/3 of total dose) of propofol was injected for 15 min while the rest of propofol was infused persistently for 1 h.Rats were sacrificed with decapitation at 0,12,24,48 h and 7 d after ischemia/reperfusion.The histological grade(HG) and neuronal density(ND) of the CA1 hippocampus were evaluated under a light microscope.The effect of propofol on GLT-1 expression of the CA1 hippocampus was observed by Western blotting.RESULTS HG was 0 in sham group and propofol control group,and grade Ⅲ in ischemia group.In propofol+brain ischemia group,the HG was 0 in three rats,and gradeⅠ in the rest.ND was 185±12 and(181±11) mm-1 in sham group and propofol control group,respectively.Almost all the pyramidal neurons in the CA1 hippocampus of ischemin group died.Compared with ischemia model group,ND was(125±14)mm-1 in propofol+brain ischemia group,and the surviving pyramidal neurons significantly increased(P<0.05).Compared with sham group at the corresponding time,GLT-1 expression significantly increased at 12 h after ischemia(0.38±0.04 vs 0.31±0.03),then gradually decreased with time,and significantly decreased at 7 d after brain ischemia(0.19±0.03 vs 0.29±0.04).GLT-1 expression of the CA1 hippocampus remained at a high level(0.47±0.05) after propofol infusion and reached 0.29±0.03 at 7 d in propofol control group.Decrease in GLT-1 expression induced by global brain ischemia was prevented by propofol infusion.At 24 and 48 h time points,GLT-1 expression of the CA1 hippocampus reached 0.45±0.04 vs 0.29±0.04 and 0.47±0.05 vs 0.27±0.04,respectively(P<0.05),as in sham group.CONCLUSION Propofol protects pyramidal neurons in the CA1 hippocampus against ischemia insult by persistent infusion before brain ischemia and up-regulates the GLT-1 expression in the CA1 hippocampus.更多还原