中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2013年
10期
1198-1201
,共4页
贺丹%陶虓嫣%廖淳杰%谢玉波
賀丹%陶虓嫣%廖淳傑%謝玉波
하단%도효언%료순걸%사옥파
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
二異丙酚%嬰兒,新生%環AMP依賴性蛋白激酶類%cAMP反應元件結閤蛋白質%海馬
이이병분%영인,신생%배AMP의뢰성단백격매류%cAMP반응원건결합단백질%해마
Propofol%Infant,newborn%Cyclic AMP-dependent protein kinases%Cyclic AMP response element-binding protein%Hippocampus
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.
目的 評價異丙酚痳醉對新生大鼠海馬蛋白激酶A(PKA)-環燐痠腺苷反應元件結閤蛋白(CREB)信號通路的影響.方法 雄性SD大鼠175隻,7日齡,體重8～15g,採用隨機數字錶法,將其分為5組(n=35):對照組(C組)、異丙酚25 mg/kg(E組)、異丙酚50 mg/kg(P2組)、異丙酚100mg/kg(B組)和異丙酚200 mg/kg(P4組).E組和P2組為單次腹腔註射異丙酚25或50 mg/kg;P3組和n組首次腹腔註射異丙酚50 mg/kg,待翻正反射恢複後,追加異丙酚50 mg/kg,直至給完總量.每組取5隻大鼠,于囌醒後即刻抽取動脈血樣行血氣分析.分彆于囌醒後2h和飼養9週時,電鏡下觀察海馬神經元超微結構,採用RT-PCR法測定海馬組織PKA mRNA和CREBmRNA的錶達,採用Westernblot法測定PKA蛋白和pCREB蛋白的錶達.結果 5組動脈血氣指標比較差異無統計學意義(P＞0.05).P2組、P3組和P4組海馬神經元齣現覈腫脹、碎裂,染色質邊集、凋亡小體,突觸數量減少,間隙增寬.與C組相比,E組、P2組、R組和P4組囌醒後2h和飼養9週時海馬組織PKA mRNA、CREBmRNA、PKA蛋白和pCREB蛋白錶達均下調(P＜0.05).結論 異丙酚痳醉對新生大鼠產生神經毒性的機製可能與抑製海馬組織PKA-CREB信號通路的激活有關.
목적 평개이병분마취대신생대서해마단백격매A(PKA)-배린산선감반응원건결합단백(CREB)신호통로적영향.방법 웅성SD대서175지,7일령,체중8～15g,채용수궤수자표법,장기분위5조(n=35):대조조(C조)、이병분25 mg/kg(E조)、이병분50 mg/kg(P2조)、이병분100mg/kg(B조)화이병분200 mg/kg(P4조).E조화P2조위단차복강주사이병분25혹50 mg/kg;P3조화n조수차복강주사이병분50 mg/kg,대번정반사회복후,추가이병분50 mg/kg,직지급완총량.매조취5지대서,우소성후즉각추취동맥혈양행혈기분석.분별우소성후2h화사양9주시,전경하관찰해마신경원초미결구,채용RT-PCR법측정해마조직PKA mRNA화CREBmRNA적표체,채용Westernblot법측정PKA단백화pCREB단백적표체.결과 5조동맥혈기지표비교차이무통계학의의(P＞0.05).P2조、P3조화P4조해마신경원출현핵종창、쇄렬,염색질변집、조망소체,돌촉수량감소,간극증관.여C조상비,E조、P2조、R조화P4조소성후2h화사양9주시해마조직PKA mRNA、CREBmRNA、PKA단백화pCREB단백표체균하조(P＜0.05).결론 이병분마취대신생대서산생신경독성적궤제가능여억제해마조직PKA-CREB신호통로적격활유관.
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.
