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| 右美托咪定对丙泊酚麻醉新生大鼠海马PI3K／Akt信号通路的影响 |
| Effects of dexmedetomidine on PI3K／Akt pathway in hippocampus of propofol anesthetized neonatal rats |
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| DOI： |
| 中文关键词: 右美托咪定 丙泊酚 磷脂酰肌醇3激酶/蛋白激酶B 海马 |
| 英文关键词: Dexmedetomidine Propofol Phosphoinositide 3 kinase/protein kinase B Hippocampal |
| 基金项目:国家自然科学基金（81373498，81060277）；广西科学研究与技术开发计划项目（桂科攻1355005-4-2）；广西高校科学技术研究项目（2013ZD014） |
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| 中文摘要: |
| 目的 探讨右美托咪定对丙泊酚麻醉新生大鼠海马磷脂酰肌醇3激酶／蛋白激酶B(phosphoinositide 3 kinase／protein kinase B,PI3K／Akt)信号通路的影响。方法 雄性SD大鼠80只,日龄7 d,体重10～15 g,随机分为八组:生理盐水组(N组)、脂肪乳剂组(I组)、二甲基亚砜(DMSO)组(D组)、丙泊酚100 mg／kg组(P组)、右美托咪定25 μg／kg+丙泊酚100 mg／kg组(PD25组)、右美托咪定50 μg／kg+丙泊酚100 mg／kg组(PD50组)、右美托咪定75 μg／kg+丙泊酚100 mg／kg组(PD75组)和LY294002 25 μg+右美托咪定75 μg／kg+丙泊酚100 mg／kg组(LYPD组)，每组10只。于大鼠苏醒2 h后,每组取5只用透射电镜观察海马神经元的形态学变化,剩余5只采用Western blot法检测海马Akt和pAkt(ser473)蛋白含量。结果八组大鼠Akt蛋白含量差异无统计学意义。P组、PD25组、PD50组、PD75组和LYPD组pAkt(ser473)蛋白含量明显低于N组(P＜0.05);PD75组和LYPD组pAkt(ser473)蛋白含量明显高于P组(P＜0.05); LYPD组pAkt(ser473)蛋白含量明显低于PD75组(P＜0.05)。N组、I组、D组大鼠海马神经元的形态结构基本正常；P组大鼠海马神经元出现细胞核明显肿胀、染色质密度降低、线粒体空泡化等细胞结构损伤表现；PD25组、PD50组、PD75组大鼠海马神经元细胞结构损伤随着右美托咪定剂量的增加而减轻；LYPD组大鼠海马神经元细胞核固缩,核膜部分溶解,染色质凝聚,线粒体明显空泡变性。结论 右美托咪定减轻丙泊酚对发育期大鼠海马神经元的损伤,其机制可能与其减弱丙泊酚对PI3K／Akt信号通路的抑制有关。 |
| 英文摘要: |
| Objective To explore the effect of dexmedetomidine on phosphoinositide 3 kinase/protein kinase B (PI3K／Akt) pathway in hippocampus of propofol anesthetized neonatal rats. Methods Eighty Sprague Dawley male rats, aged 7 days, weighing 10-15 g, were randomly divided into 8 groups (n=10 each): normal saline group (group N), DMSO group (group D), intralipid group (group I), propofol group (group P), dexmedetomidine 25 μg／kg, 50 μg／kg and 75 μg／kg + propofol 100 mg／kg groups (groups PD25, PD50 and PD75), LY294002 25 μg + dexmedetomidine 75 μg／kg + propofol 100 mg／kg group (group LYPD). The hippocampus of rats in all groups were taken 2 h after the animals fully awake. The ultrastructure of hippocampal neurons was observed by transmission electron microscope. The pAkt(ser473) protein and Akt protein in the hippocampus were evaluated by Western blot analysis. Results There was no significant difference in the expression of Akt protein among the eight groups. Compared with group N, the expression of pAkt (ser473) protein was significantly down regulated in groups P, PD25, PD50, PD75 and LYPD (P＜0.05). Compared with group P, the expression of pAkt (ser473) protein was increased significantly in groups PD75 and LYPD (P＜0.05). Compared with group PD75, the expression of pAkt (ser473) protein was significantly down regulated in group LYPD (P＜0.05). The structure of hippocampal neurons was normal in groups N, I and D. Nuclear nuclei swelling, chromatin decreasing and mitochondrion vacuolar degeneration were observed in group P while improved gradually with dexmedetomidine in a dose dependent manner in groups PD25, PD50 and PD75. Neurons karyopyknosis, partial dissolution of nuclear membrane, chromatin condensation, mitochondria vacuolar degeneration were observed in group LYPD. Conclusion Dexmedetomidine pretreatment provides neuroprotection against propofol induced hippocampal destruction by preserving PI3K／Akt pathway activity in the developing brains. |
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