艾司氯胺酮对阻塞性睡眠呼吸暂停综合征大鼠认知功能与Shh/Ptch1通路的影响

doi:10.3969/j.issn.1006-6233.2025.11.04

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摘要 目的: 探究艾司氯胺酮(esketamine,ESK)对阻塞性睡眠呼吸暂停综合征(OSAS)大鼠海马组织损伤、认知功能的影响及对音猬因子(Shh)/补缀同源物1(Ptch1)通路的调控作用。方法: 将72只SD雄性大鼠随机分为对照组(Control组)、模型组(OSAS组)、艾司氯胺酮低剂量组(ESK-L组)、艾司氯胺酮高剂量组(ESK-H组)、Shh/Ptch1通路激活剂组(Purmorphamine组)、艾司氯胺酮高剂量+Shh/Ptch1通路抑制剂组(ESK-H+Cyclopamine组),每组12只。除Control组外,其余组大鼠均构建OSAS模型。检测各组大鼠认知能力(Morris水迷宫实验)和血氧饱和度(血氧监护仪),取大鼠海马组织分别检测炎症因子和氧化应激因子水平(ELISA法)、海马组织病理变化(HE染色)、神经元凋亡情况(TUNEL法)、神经元超微结构(透射电镜法)、Shh/Ptch1通路蛋白表达(Western blot法)。结果: OSAS组大鼠血氧饱和度、平台停留时间占比、海马组织IL-10含量、SOD活性及Shh/Ptch1通路蛋白表达量明显降低,逃避潜伏期、海马组织IL-6及MDA含量、神经元凋亡率明显升高(P<0.05);ESK可显著提高OSAS大鼠血氧饱和度、平台停留时间占比、海马组织IL-10含量、SOD活性及Shh/Ptch1通路蛋白表达量,降低逃避潜伏期、海马组织IL-6及MDA含量和神经元凋亡率,指标变化呈ESK剂量效应(P<0.05);Cyclopamine可逆转ESK对OSAS大鼠海马组织损伤及认知功能的改善作用(P<0.05)。结论: ESK可抑制海马组织炎症和氧化应激反应、减轻神经元凋亡和海马组织病理损伤,提高认知能力,其作用机制可能是通过激活Shh/Ptch1通路实现的。

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	谷昆峰
	马文女
	董慧咏
	赵建辉

关键词 ：艾司氯胺酮, 阻塞性睡眠呼吸暂停综合征, 海马组织, 认知功能, Shh/Ptch1通路

Abstract：Objective: To explore the effects of Esketamine (ESK) on hippocampal tissue injury and cognitive function in rats with obstructive sleep apnea syndrome (OSAS), as well as its regulatory role in the sonic hedgehog factor (Shh)/complement homologous 1 (Ptch1) pathway. Methods: Totally 72 male SD rats were stochastically separated into a control group, a model group (OSAS group), a low-dose ESK group (ESK-L group), a high-dose ESK group (ESK-H group), a Shh/Ptch1 pathway activator group (Purmorphoamine group), and a high-dose ESK+Shh/Ptch1 pathway inhibitor group (ESK-H+Cyclopamine group), each with 12 rats. Except for the control group, OSAS models were constructed in all other groups. The cognitive ability (Morris water maze test) and blood oxygen saturation (blood oxygen monitor) of rats in each group were tested. The hippocampal tissue of rats was taken to detect the inflammatory factors and oxidative stress factors (ELISA method), pathological changes in hippocampal tissue (HE staining), neuronal apoptosis (TUNEL method), neuronal ultrastructure (transmission electron microscopy method), and Shh/Ptch1 pathway proteins (Western blot method). Results: The OSAS group had prominently lower blood oxygen saturation, proportion of plateau dwelling time, IL-10 content, SOD activity, and Shh/Ptch1 pathway proteins in hippocampal tissue, and prominently higher escape latency, IL-6 and MDA contents in hippocampal tissue, and neuronal apoptosis rate (P<0.05). ESK could prominently increase blood oxygen saturation, proportion of plateau dwelling time, IL-10 content, SOD activity, and Shh/Ptch1 pathway proteins in hippocampal tissue, and prominently reduce escape latency, IL-6 and MDA contents in hippocampal tissue, and neuronal apoptosis rate. The changes in these indicators showed a dose-response relationship with ESK (P<0.05). Cyclopamine could reverse the improvement effects of ESK on hippocampal tissue damage and cognitive function in OSAS rats (P<0.05). Conclusion: ESK can inhibit inflammation and oxidative stress response in hippocampal tissue, alleviate neuronal apoptosis and pathological damage in hippocampal tissue, and improve cognitive ability. Its mechanism of action may be achieved by activating the Shh/Ptch1 pathway.

Key words： Esketamine Obstructive sleep apnea syndrome Hippocampal tissue Cognitive function Shh/Ptch1 pathway

基金资助:石家庄市科学技术研究与发展指导计划,(编号:191460443)

引用本文:

谷昆峰, 马文女, 董慧咏, 赵建辉. 艾司氯胺酮对阻塞性睡眠呼吸暂停综合征大鼠认知功能与Shh/Ptch1通路的影响[J]. 河北医学, 2025, 31(11): 1780-1786.
GU Kunfeng, MA Wennv, DONG Huiyong, et al. The Effect of Esketamine on Cognitive Function and Shh/Ptch1 Pathway in Rats with Obstructive Sleep Apnea Syndrome. HeBei Med, 2025, 31(11): 1780-1786.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.11.04 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I11/1780

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