异丙酚麻醉对新生大鼠海马PKA-CREB信号通路的影响  

Effects of propofol anesthesia on hippocampal PKA-CREB signaling pathway in neonatal rats

作　　者：贺丹[1] 陶虓嫣[1] 廖淳杰[2] 谢玉波[1] 

机构地区：[1]广西医科大学第一附属医院麻醉科,530021 [2]广西壮族自治区人民医院麻醉科

出　　处：《中华麻醉学杂志》2013年第10期1198-1201,共4页Chinese Journal of Anesthesiology

摘　　要：目的 评价异丙酚麻醉对新生大鼠海马蛋白激酶A（PKA）-环磷酸腺苷反应元件结合蛋白（CREB）信号通路的影响.方法 雄性SD大鼠175只,7日龄,体重8～15g,采用随机数字表法,将其分为5组（n=35）：对照组（C组）、异丙酚25 mg/kg（E组）、异丙酚50 mg/kg（P2组）、异丙酚100mg/kg（B组）和异丙酚200 mg/kg（P4组）.E组和P2组为单次腹腔注射异丙酚25或50 mg/kg;P3组和n组首次腹腔注射异丙酚50 mg/kg,待翻正反射恢复后,追加异丙酚50 mg/kg,直至给完总量.每组取5只大鼠,于苏醒后即刻抽取动脉血样行血气分析.分别于苏醒后2h和饲养9周时,电镜下观察海马神经元超微结构,采用RT-PCR法测定海马组织PKA mRNA和CREBmRNA的表达,采用Westernblot法测定PKA蛋白和pCREB蛋白的表达.结果 5组动脉血气指标比较差异无统计学意义（P＞0.05）.P2组、P3组和P4组海马神经元出现核肿胀、碎裂,染色质边集、凋亡小体,突触数量减少,间隙增宽.与C组相比,E组、P2组、R组和P4组苏醒后2h和饲养9周时海马组织PKA mRNA、CREBmRNA、PKA蛋白和pCREB蛋白表达均下调（P＜0.05）.结论 异丙酚麻醉对新生大鼠产生神经毒性的机制可能与抑制海马组织PKA-CREB信号通路的激活有关.Objective To evaluate the effects of propofol anesthesia on hippocampal protein kinase A （PKA）-cAMP response element binding protein （CREB） signaling pathway in neonatal rats.Methods One hundred and seventy-five male Sprague-Dawley rats,aged 7 days,weighing 8-15 g,were randomly divided into 5 groups （n =35 each） using a random number table：control group （C group） and propofol 25,50,100 and 200 mg/kg groups （P~ groups）.Groups P1 and P2 received intraperitoneal propofol 25 and 50 mg/kg,respectively.Groups P3 and P4 received intraperitoneal propofol 100 and 200 mg/kg,respectively,and after righting reflex completely recovered,an increment of propofol 50 mg/kg was given until the total amount was finished.Five animals in each group were chosen and arterial blood samples were obtained immediately after the animals were fully awake for blood gas analysis.Five animals in each group were chosen at 2 h after fully awake and the age of 9 weeks,the rats were sacrificed and their brains were removed for microscopic examination of the ultrastructure of hippocampal neurons and for determination of PKA mRNA,CREB mRNA,PKA protein and pCREB protein in hippocampus （using RT-PCR and Western blot analysis）.Results There was no significant difference in the indexes of blood gas analysis anong the five groups （P ＞ 0.05）.Nuclear swelling and fragmentation,chromatin condensation,apoptotic bodies,decreased number of synapses and widened synaptic space were observed in P2,P3 and P4 groups.Compared with group C,the expression of PKA mRNA,CREB mRNA,PKA protein and pCREB protein was significantly down-regulated at 2 h after fully awake and the age of 9 weeks in P1,P2,P3 and P4 groups （P ＜ 0.05）.Conclusion The mechanism by which propofol anesthesia induces neurotoxicity in neonatal rats may be related to inhibition of the activity of PKA-CREB signaling pathway.

关 键 词：二异丙酚 婴儿 新生 环AMP依赖性蛋白激酶类 CAMP反应元件结合蛋白质 海马 

分 类 号：R726.1[医药卫生—儿科]