国际麻醉学与复苏杂志   2014, Issue (4): 6-6
    
右美托咪啶对脑膜瘤患者磷脂肌醇3激酶/蛋白激酶B信号通路的影响
张喜洋, 高瑞萍, 石翊飒, 韩昀, 黄生辉, 路文胜, 白武民, 杨小华1()
1.甘肃省兰州大学第二医院
The effect of dexmedetomidine on phosphatidylinositol 3 kinase/protein kinase B signal pathway during perioperative period in patients with meningioma
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摘要:

目的 探讨盐酸右美托咪定(dexmedetomidine, Dex)对脑膜瘤患者磷脂肌醇3激酶(phosphatidylinositol 3 kinase, PI3K)及蛋白激酶B(protein kinase B, PKB/Akt)表达的影响。 方法 选择择期行脑膜瘤切除术患者45例,年龄45岁~65岁,体重55 kg~65 kg,美国麻醉医师协会(ASA)分级Ⅱ或Ⅲ级,采用随机数字表法将患者分为3组(每组15例):对照组(C组),Dex低剂量组(D1),Dex高剂量组(D2),D1和D2组于常规诱导前10 min静脉输注Dex负荷量1 μg/kg,继之分别以0.2 μg·kg-1·h-1和0.5 μg·kg-1·h-1持续输注至术毕前30 min,C组给予等容量的生理盐水。3组术中维持脑电双频指数(bispectral index, BIS)值在40~49之间,分别于麻醉诱导前(T1)、取出肿瘤时(T2)、拔管时(T3)、术后24 h(T4)采集静脉血样,测定血清中PI3K及Akt的浓度,且分别于T1、T2、T3采集桡动脉及颈静脉球部的血样行血气分析,记录并计算动脉血氧含量(arterial oxygen content, CaO2)、脑动脉-静脉血氧含量差(cerebral arterial venous oxygen content difference, Da-jvO2)和脑氧摄取(cerebral extraction of oxygen, CEO2)。  结果 与T1时比较,3组T2~T4时血清PI3K、Akt浓度及CEO2升高(P<0.05);T2~T4时D2组血清PI3K浓度[(5.5±0.4)、(6.3±0.5)、(7.1±0.6) μg/L]及Akt浓度[(0.351±0.024)、(0.414±0.023)、(0.472±0.033) μg/L]与C组血清PI3K浓度[(5.9±0.5)、(6.8±0.6)、(8.2±0.5) μg/L]及Akt浓度[(0.401±0.032)、(0.482±0.050)、(0.593±0.058) μg/L]比较差异有统计学意义(P<0.05);T2、T3时D1组CEO2[(0.33±0.04)%、(0.30±0.04)%]和D2 组CEO2[(0.32±0.04)%、(0.26±0.04)%]与C组CEO2[(0.36±0.03)%、(0.34±0.03)%]比较差异有统计学意义(P<0.05),但D2 组降低更为显著(P<0.01)。 结论 静脉输注Dex可对围术期脑膜瘤患者发挥脑保护作用,其机制可能与降低血PI3K及Akt的浓度,下调PI3K/Akt信号通路及CEO2有关。

关键词: 盐酸右美托咪啶; 神经保护; 脑膜瘤; 脑氧摄取
Abstract:

Objective To evaluate the effect of dexmedetomidine(Dex) on Phosphatidylinositol 3 kinase (PI3K) and protein kinase B(PKB/Akt) concentration during perioperative period in patients with meningioma. Methods Forty-five ASAⅡor Ⅲ patients with meningioma scheduled for elective intracranial tumor recection were randomly divided into 3 groups(n=15): control group(group C),low-dose Dex group 0.2 μg·kg-1·h-1(group D1), high dose Dex group 0.5 μg·kg-1·h-1(group D2). Dex was intravenously infused 10 min before induction at the dose of 1 μg/kg, followed by constant speed infusion at 0.2 μg·kg-1·h-1 and 0.5 μg·kg-1·h-1 in group D1 and D2 respectively until 30 min before the end of the operation. Group C received the same volume of saline. Bispectral index(BIS) was maintained at 40-49. Venous blood samples were taken for determination of serum concentrations of Akt and PI3K respectively at the time before induction(T1), removal of tumor(T2), extubation(T3) and 24 h after operation(T4). Blood samples were also collected from radial artery and jugular venous bulb for blood gas analysis to calculate the arterial oxygen content(CaO2),cerebral arterial venous oxygen content difference cerebral arterial venous oxygen content difference(Da-jvO2) and cerebral extraction of oxygen(CEO2). Results Compared with T1, the serum concentration of Akt and PI3K and CEO2 significantly increased at T2-T4 in the all groups(P<0.05). There was significant difference between group C and group D2 in the concentration of PI3K and Akt at T2-T4(P<0.05), PI3K in group C were[(5.9±0.5),(6.8±0.6),(8.2±0.5) μg/L], while that of group D2 were[(5.5±0.4),(6.3±0.5),(7.1±0.6) μg/L]respectively at T2-T4. Akt in serum in group C were[(0.401±0.032),(0.482±0.050),(0.593±0.058) μg/L], while that of group D2 were[(0.351±0.024),(0.414±0.023),(0.472±0.033) μg/L] respectively at T2-T4. There was significant difference among the three groups in CEO2 at T2-T3(P<0.05), CEO2 in group C were[(0.36±0.03)%,(0.34±0.03)%],while that of group D1 were[(0.33±0.04)%,(0.30±0.04)%], and group D2 were[(0.32±0.04)%,(0.26±0.04)%] respectively at T2-T3. Conclusions Intraoperative infusion of dexmedetomidine may play a protective effect on patients with meningioma. The mechanism may be associated with lowering plasma PI3K and Akt and cerebral oxygen uptake rate.

Key words: Dexmedetomidine; Neuroprotection; Meningioma; Cerebral extraction of oxygen