右美托咪定对大鼠局灶性脑缺血/再灌注损伤的保护作用及机制

被引：10

作者：

王灿灿

余健

机构：

[1] 泰兴,扬州大学附属泰兴医院麻醉科

来源：

中华行为医学与脑科学杂志 | 2016年 / 25卷 / 02期

关键词：

右美托咪定; 大脑中动脉栓塞; PI3K; Akt; 内皮型一氧化氮合酶;

D O I：

暂无

中图分类号：

R614 [麻醉学];

学科分类号：

100217 [麻醉学];

摘要：

目的研究右美托咪定(dexmedetomidine, Dex)对大鼠脑缺血/再灌注损伤的神经保护作用及其相关机制。方法雄性SD大鼠, 采用右侧大脑中动脉栓塞90 min, 再灌注24 h建立局灶性脑缺血/再灌注模型(I/R组), 缺血即刻股静脉泵注Dex(15 μg·kg–1), 根据需要在缺血前给予侧脑室注射PI3K阻断剂LY294002(LY, 10 mM, 10 μl)或内皮型一氧化氮合酶(eNOS)阻断剂L-NIO(1 mg·kg–1, 10 μl)。测定再灌注24 h后Dex对神经功能缺损评分, 脑水肿, 大脑梗死体积, 缺血区神经元存活, 缺血区脑组织p-Akt (Ser473)、p-eNOS(Ser1177)的蛋白表达。结果 Dex处理组大鼠神经功能缺损评分、大脑梗死体积、脑水肿程度均显著低于单纯I/R组[(2.3±0.4)分vs (3.9±0.6)分, (19.3±3.5)%vs (40.5±5.4)%, (61.8±8.1)%vs (76.3±8.5)%, 均P<0.05], Dex组缺血侧海马CA1区和皮质神经细胞存活数量均显著高于单纯I/R组[(136.5±15.8)/mmvs (53.5±7.9)/mm, (253.8±26.4)/mm3vs (112.5±14.6)/mm3, 均P<0.01]。Dex对缺血侧的脑保护作用可被LY和L-NIO预处理明显抑制(P<0.05)。此外, LY组脑缺血区p-Akt、p-eNOS的表达均显著低于Dex处理组[(3.94±0.45)vs (0.85±0.21), (2.14±0.25)vs (0.79±0.29), 均P<0.01];而L-NIO组脑缺血区p-Akt的表达与Dex组比较差异无统计学意义[(3.76±0.33)vs(3.94±0.45), P>0.05]。结论 Dex可以通过上调PI3K/Akt, 促进eNOS磷酸化激活减轻大鼠局灶性脑缺血/再灌注损伤。

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