“脂质学说”是吸入全麻药物的麻醉机制之一,由于吸入全麻药物需要穿破细胞膜表面的脂筏进入细胞内产生麻醉作用,因此,吸入麻醉药是否对老年大脑的脂代谢产生影响是一个值得研究的科研问题。联合课题组运用上述相同的老年狨猴麻醉模型,对七氟烷麻醉的老年狨猴的前额叶皮层进行了脂质组学分析。发现七氟醚对老年狨猴的大脑前额叶皮层脂质代谢影响非常轻微,甚至可以忽略不计,同时,脂质代谢途径也没有受到影响(Frontiers In Molecular Neuroscience,2022)。
2021年7月2号,国际麻醉学领域著名期刊British Journal of Anaesthesia(中科院分区1区;影响因子11.719;)发表了联合课题组科研成果“Sevoflurane enhanced glycolysis and lactate production in the brain of aged marmosets”,首次发现临床最常用的吸入麻醉药七氟烷可以引起老年非人灵长类动物狨猴脑内糖酵解的激活和乳酸的升高。在本研究中,联合课题组首先发现年龄大于65岁的接受全身麻醉时间大于6小时的头颈颌面部肿瘤患者,其术后血中的乳酸升高。由于血液流经全身脏器,不能推测出脑内的乳酸是否同样增高。随后,课题组对老年狨猴(>8岁)进行了单次6小时的临床浓度七氟烷(1.5-2%)麻醉,并在麻醉后即刻获取前额叶皮质进行检测,发现老年狨猴脑内糖酵解的激活和乳酸的升高。结合以前文献15, 16,相对于静脉麻醉药丙泊酚,这可能是吸入麻醉药所特有的能力。
乳酸是大脑中重要的能量供体,同时兼具神经递质的作用17。鉴于乳酸在大脑内的重要性,我们的研究有助于理解和拓展一波本专业领域中临床问题:1,推进脑乳酸在术后谵妄中的机制研究。最近发表在British Journal of Anaesthesia的临床研究发现术后谵妄患者脑脊液中乳酸水平显著升高,提示脑内的乳酸升高可能和术后谵妄相关18。由于乳酸是脑内重要的提供能量的底物同时兼具有神经递质的功能,因此乳酸在术后谵妄中的作用和机制值得我们高度重视。2,推进从脑代谢角度研究吸入麻醉的脑电图特点。比如脑电图监测发现吸入麻醉药可以诱发癫痫波19,而血中乳酸的升高是预判癫痫发作的生物标记物20。同时动物实验表明,通过抑制乳酸脱氢酶进而减少乳酸的生成可以阻断体外培养的神经元兴奋(一种体外惊厥模型),也能抑制动物惊厥的发生21。3,推进从脑代谢角度研究全麻机制,乳酸是神经元的能量底物,也是重要的神经递质,乳酸增高可以使邻近的锥体细胞去极化,乳酸是否牵涉进全麻的机制值得进一步研究。4,大脑内的神经细胞多样且各自代谢特点不尽一样,因此,全身麻醉下的脑代谢状态值得深入研究。再者麻醉教材包括现代麻醉学等里面对围术期脑代谢介绍不多,且将大脑视为一个整体来看。但大脑里面包含各种类型的神经细胞,不同麻醉药物对不同神经细胞代谢方式的影响应该有更多研究关注,丰富我们的麻醉教材。5,推进从脑代谢角度研究吸入麻醉药与脑保护的研究。比如创伤性脑损伤时,乳酸的能量供给对神经元的能量代谢非常重要22,相对于静脉全麻药物,吸入麻醉药的脑保护优势特点是否和其能够引起乳酸升高相关?6,推进从脑代谢角度研究吸入麻醉药与术后肿瘤患者预后。比如肿瘤细胞主要依靠糖酵解和乳酸生成为能量,吸入全麻药物对胶质瘤细胞的促增殖侵袭效应23是否和其加强糖酵解促进乳酸生成相关?7,糖尿病患者存在葡萄糖代谢障碍,大脑可能更加依赖脑内的糖酵解24。吸入全身麻醉下,糖尿病患者的脑代谢状态需要进一步去研究。
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