α-硫辛酸对幼年大鼠全麻后远期认知功能障碍的改善作用及机制研究

A new research has shown that general anesthesia in infants and young children can lead to cognitive dysfunction on the developing brain in some cases.The brain cell death induces cognitive and behavioral disorder directly ,which results in poorer performance on tests of memory, attention and learning ,even then it will influence the young teenagers' physical and mental development . Recent studies have suggested that disturbance in mitochondrial integrity and function , and activation of the intrinsic apoptotic pathway could be the earliest triggering events of neuro-apoptosis caused by general anesthesia, and this process can be inhibited by the active PI3K/Akt signal path. The protective effect ofα-Lipoic acid (LA) against Alzheimer , parkinsonism and ischemic brain injury has been confirmed . However, there is no home and abroad report about the protective effect of LA against general anesthesia-induced cognitive dysfunction on the developing brain. The results of our early experiment showed that LA depresses general anesthesia-induced apoptosis on the developing rat brain with the phosphorylation level of Akt and GSK-3? increasing .So we assume that LA may be reduce the severity of general anesthesia-induced cognitive dysfunction on the developing rat brain and the mechanism possibly involve activation of the PI3K/Akt signaling pathway.

近期的研究表明，婴幼儿接受全麻，会引起中枢神经元的线粒体依赖性凋亡，造成远期的认知功能障碍，发现和鉴定可以预防、治疗该不良反应的药物，是目前的迫切任务。然而，迄今对此方面仍然知之甚少。我们的前期研究表明：α-硫辛酸（LA）可显著改善七氟醚联合全麻所致幼年大鼠的学习、记忆能力，但其机制还有待进一步探讨。为此，我们提出如下研究假说：LA通过激活PI3K/Akt信号通路，阻断线粒体依赖性凋亡通路、抑制神经元凋亡，最终改善全麻引起的幼年大鼠认知功能障碍。为了验证这一假说，我们将通过SD大鼠及其原代皮层细胞，采用Morris水迷宫、MTT、TUNEL和Western-blot等方法，从细胞、组织和动物整体水平上探讨LA在改善幼年大鼠全麻后认知功能中的重要作用，明确LA通过激活PI3K/Akt通路，抑制神经元凋亡的机制，为发现防治全麻所致婴幼儿远期认知功能障碍的药物提供前瞻性思路。

七氟烷作为吸入性全麻药物已被广泛应用，尤其运用于小儿以及婴儿的麻醉中。近期的许多研究关注于全麻药物引起的脑细胞凋亡。这一问题增加了对于全麻药物导致凋亡的神经毒性的关注，特别是对婴幼儿远期认知功能影响的关注。我们的研究通过Morris水迷宫，western blotting和免疫组化实验初步证实了α-硫辛酸在抑制七氟烷引起的神经细胞凋亡中所起的关键作用及其机制，研究结果显示α-硫辛酸可能降低了七氟烷所致远期认知功能障碍的发生率。本研究阐明了α-硫辛酸对预防和治疗七氟烷全麻所致的远期认知功能障碍有潜在的临床意义。