Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China.
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China.
J Mol Neurosci. 2023 Aug;73(7-8):549-562. doi: 10.1007/s12031-023-02135-w. Epub 2023 Jun 30.
Cerebral ischemic stroke (CIS) has become the second leading cause of death worldwide, which is largely related to cerebral ischemia reperfusion injury (CIRI). Surgical intervention is a reliable treatment for CIS, which predictably causes cerebral reperfusion. Therefore, the choice of anesthetic drugs has important clinical significance. Isoflurane (ISO), one of the most used anesthetics, attenuates cognitive impairment and has brain protective effects. However, the role of isoflurane in regulating autophagy and its regulatory mechanism on inflammation in CIRI are still unclear. The middle cerebral artery occlusion (MCAO) method was used to establish a rat model of CIRI. After 24 h of reperfusion, all rats were evaluated by mNSS scoring and dark avoidance experiment. Western blotting and immunofluorescence were used to examine the expression of key proteins. Compared with the sham group, the MCAO group showed increased neurobehavioral scores and decreased cognitive memory function (P < 0.05). As for the ISO-treated MCAO rats, the neurobehavioral score was significantly decreased, the expression of AMPK, ULK1, Beclin1, and LC3B was significantly increased, and the cognitive and memory functions were also significantly improved (P < 0.05). After inhibition of autophagy pathway or key protein AMPK in autophagy, neurobehavioral scores and protein expression of NLRP3, IL-1β, and IL-18 were significantly increased (P < 0.05). Isoflurane post-treatment may enhance autophagy by activating the AMPK/ULK1 signaling pathway and further inhibit the release of inflammatory factors from NLRP3 inflammasomes, thereby ameliorating neurological function and cognitive impairment and exerting a protective effect on the brain in CIRI rats.
脑缺血性脑卒中（CIS）已成为全球第二大致死原因，这在很大程度上与脑缺血再灌注损伤（CIRI）有关。手术干预是治疗 CIS 的可靠方法，可预测性地引起脑再灌注。因此，麻醉药物的选择具有重要的临床意义。异氟烷（ISO）是最常用的麻醉剂之一，可减轻认知障碍并具有脑保护作用。然而，异氟烷在调节自噬中的作用及其对 CIRI 中炎症的调节机制尚不清楚。采用大脑中动脉闭塞（MCAO）方法建立大鼠 CIRI 模型。再灌注 24 小时后，通过 mNSS 评分和暗回避实验对所有大鼠进行评估。使用 Western blot 和免疫荧光技术检测关键蛋白的表达。与假手术组相比，MCAO 组的神经行为评分升高，认知记忆功能降低（P<0.05）。对于 ISO 处理的 MCAO 大鼠，神经行为评分显著降低，AMPK、ULK1、Beclin1 和 LC3B 的表达显著增加，认知和记忆功能也显著改善（P<0.05）。在自噬途径或自噬关键蛋白 AMPK 被抑制后，神经行为评分和 NLRP3、IL-1β 和 IL-18 的蛋白表达显著增加（P<0.05）。异氟烷后处理可能通过激活 AMPK/ULK1 信号通路增强自噬，进一步抑制 NLRP3 炎性小体中炎症因子的释放，从而改善 CIRI 大鼠的神经功能和认知障碍，发挥脑保护作用。
