Department of Anesthesiology, Yantaishan Hospital, Yantai 264000, China.
Department of Anesthesiology , Feicheng People's Hospital, Feicheng 271600, China.
Neurosci Lett. 2023 Mar 28;801:137164. doi: 10.1016/j.neulet.2023.137164. Epub 2023 Mar 1.
We aimed to study the influence of sevoflurane on the nucleotide-binding domain and Leucine-rich repeat protein 3 (NLRP3) pathways in rats with cerebral ischemia/reperfusion (I/R) injury.
Sixty Sprague-Dawley rats were equally divided into five groups randomly: sham-operated, cerebral I/R, sevoflurane (Sevo), NLRP3 inhibitor-treated (MCC950), and sevoflurane and NLRP3 inducer-treated groups. Rats' neurological functions were assessed using Longa scoring after 24 h of reperfusion, after which they were sacrificed, and cerebral infarction area was determined by triphenyl tetrazolium chloride staining. Pathological changes in damaged portions were assessed using hematoxylin-eosin and Nissl staining, and cell apoptosis was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in brain tissues were determined using enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) levels were analyzed using a ROS assay kit. Protein levels of NLRP3, caspase-1, and IL-1β were determined by western blot.
Neurological function scores, cerebral infarction areas, and neuronal apoptosis index were decreased in the Sevo and MCC950 groups than in the I/R group. IL-1β, TNF-α, IL-6, IL-18, NLRP3, caspase-1, and IL-1β levels decreased in the Sevo and MCC950 groups (p < 0.05). ROS and MDA levels increased, but SOD levels increased in the Sevo and MCC950 groups than in the I/R group. NLPR3-inducer nigericin eliminated the protective effects of sevoflurane on cerebral I/R injury in rats.
Sevoflurane could alleviate cerebral I/R-induced brain damage by inhibiting the ROS-NLRP3 pathway.
研究七氟醚对脑缺血再灌注（I/R）损伤大鼠核苷酸结合寡聚化结构域样受体蛋白 3（NLRP3）通路的影响。
60 只 Sprague-Dawley 大鼠随机均分为 5 组：假手术组、脑 I/R 组、七氟醚（Sevo）组、NLRP3 抑制剂（MCC950）处理组和 Sevo 与 NLRP3 诱导剂处理组。再灌注 24 h 后，Longa 评分评估大鼠神经功能，处死大鼠，氯化三苯基四氮唑染色测定脑梗死面积。苏木精-伊红和尼氏染色评估损伤部位的病理变化，末端脱氧核苷酸转移酶介导的缺口末端标记染色检测细胞凋亡。酶联免疫吸附试验测定脑组织中白细胞介素 1β（IL-1β）、肿瘤坏死因子 α（TNF-α）、白细胞介素 6（IL-6）、白细胞介素 18（IL-18）、丙二醛（MDA）和超氧化物歧化酶（SOD）水平。活性氧（ROS）水平采用 ROS 检测试剂盒分析。Western blot 法测定 NLRP3、半胱氨酸天冬氨酸蛋白酶 1（caspase-1）和 IL-1β蛋白水平。
与 I/R 组相比，Sevo 组和 MCC950 组的神经功能评分、脑梗死面积和神经元凋亡指数降低。Sevo 组和 MCC950 组的 IL-1β、TNF-α、IL-6、IL-18、NLRP3、caspase-1 和 IL-1β水平降低（p<0.05）。Sevo 组和 MCC950 组的 ROS 和 MDA 水平升高，SOD 水平升高。NLRP3 诱导剂 Nigericin 消除了七氟醚对大鼠脑 I/R 损伤的保护作用。
七氟醚通过抑制 ROS-NLRP3 通路减轻脑 I/R 引起的脑损伤。
