谢恒韬　潘侠　何旋

[摘要] 目的 观察不同剂量的丙泊酚对大鼠下丘脑垂体、海马Akt以及海马淀粉样β蛋白的影响。 方法 雄性SPF级SD大鼠24只，采用大鼠尾部静脉注射的方式，较小剂量分次尾部静脉注射的方法，注射共3次。每次剂量为10 mg/mL，根据累积剂量分为丙泊酚Ⅰ组（10 mg/mL），丙泊酚Ⅱ组（20 mg/mL）和丙泊酚Ⅲ组（30 mg/mL），对照组不进行麻醉处理，每组各6只。脑电图仪检测大鼠的脑电信号，HE染色观察大鼠下丘脑弓状核神经元和垂体促性腺细胞病理学变化，Western blot检測各组大鼠海马Akt及淀粉样β蛋白（Aβ）表达水平。结果 与对照组比较，棘波、α波和β波随着丙泊酚剂量的增加而显著增加（P < 0.05），δ波随着丙泊酚剂量的的增加而显著降低（P < 0.05）；对照组的下丘脑弓状核神经元密度和分布正常，腺垂体细胞整体数目多，细胞间有丰富的窦状毛细血管，细胞排列规则；丙泊酚Ⅰ组的大鼠弓状核神经元无明显病变，腺垂体细胞也并无出现明显的降低；随着剂量的增加，丙泊酚Ⅱ组和丙泊酚Ⅲ组下丘脑神经元细胞和垂体细胞数量明显减少，核膜界限不清，细胞排列不规则增加；Western blot结果显示，与对照组相比，随着丙泊酚剂量的增加，海马内的Akt蛋白表达呈降低趋势（P < 0.01），Aβ表达明显增加（P < 0.01）。 结论 低剂量丙泊酚不足以促使下丘脑和垂体发生病变，当丙泊酚剂量增大时，下丘脑和腺垂体反馈作用增强，导致病理变化的发生，丙泊酚麻醉对β淀粉样蛋白沉积作用可能是通过抑制Akt途径实现的。

[关键词] 丙泊酚；下丘脑；垂体；淀粉样β蛋白

[中图分类号] R614 [文献标识码] A [文章编号] 1673-7210（2017）07（a）-0024-04

[Abstract] Objective To observe the effects of different Propofol anesthesia doses on rat hypothalamus， pituitary， hippocampus Akt and amyloid beta protein （Aβ）. Methods 24 SPF grade male rats were used by method of low-dose tail intravenous injection （10 mg/mL） for 3 times. The rats were divided into 4 groups by methods of cumulative dose， control， Propofol group Ⅰ （10 mg/mL）， Propofol group Ⅱ （20 mg/mL） and Propofol group Ⅲ （30 mg/mL）， respectively. No anaesthetic management was given in control group， with 6 rates in each group. Electroencephalogram was detected by electroencephalograph； the pathology of rat hypothalamic arcuate nucleus neurons and pituitary gonadotropin cell was observed by HE staining. Western blot detection was used to detect the expression of the Akt and Aβ. Results Compared with the control group， the spike wave， α wave and β wave increased significantly with the increase of the Propofol dose （P < 0.05）， and the δ wave decreased significantly with the Propofol dose increasing （P < 0.05）. The density and distribution of hypothalamic arcuate nucleus were normal in the control group， with the large whole number of adenohypophysis cells， abundant sinusoid capillary between cells， and the cells were arranged regularly； no obvious lesions of rats arcuate nucleus neuron in Propofol group Ⅰ was observed， as well as no obvious reduction in adenohypophysis cells. With increasing of dose of anesthesia， the number of hypothalamic neuron cells and adenohypophysis cells reduced significantly， with unclear boundary of nuclear membrane and an increase in the number of irregular arrangement cells. The Western blot results suggested that with increasing of the Propofol dose， the Akt hippocampus protein expression reduced dramatically （P < 0.01） while Aβ expression increased significantly （P < 0.01） in anesthesia group comparing with control. Conclusion Low-dose Propofol anesthesia can not cause lesions in hypothalamus and hypophysis， but their feedback effects enhanced with Propofol dose increasing， causing pathological changes. The deposition effects of Propofol anesthesia on Aβ may be achieved by inhibiting Akt pathway.

[Key words] Propofol； Hypothalamus； Pituitary； Hippocampus amyloid β protein

术后认知功能障碍是麻醉手术患者常见的神经系统并发症。海马在机体的学习、记忆及意识行为等生理过程中起到重要的作用[1-2]，麻醉药对海马的结构和功能有显著的影响作用，其通过调节GABA-A受体抑制长时程增强，进而达到麻醉时的遗忘状态。有研究发现丙泊酚及其他全麻药可使在体记录到的海马脑电反应和诱发电位产生明显的剂量依赖性改变[3-4]。此外，丘脑也是麻醉药发挥作用的主要靶位，皮质环路在麻醉药对感觉信息处理产生影响[5]，而脑下垂体在功能上与下丘脑紧密相连，所以一般将下丘脑与垂体看作为一个完整的功能系统，对靶器官的功能活动进行调节[6-8]。本研究通过不同剂量的丙泊酚麻醉大鼠，观察不同剂量丙泊酚对大鼠下丘脑和垂体的形态学影响，以及大鼠海马内Aβ表达的变化，并研究其可能的作用途径。……