2021 年第 12 期 第 16 卷

右美托咪定对小鼠反复缺血再灌注脑损伤时NOD样受体蛋白3炎症小体表达的影响

Effects of dexmedetomidine on the expression of NOD-like receptor protein 3 inflammasomes in mice with repeated ischemia-reperfusion brain injury

作者：王佳佳1张国庆2顾婷婷1王世全1

英文作者：Wang Jiajia1 Zhang Guoqing2 Gu Tingting1 Wang Shiquan1

单位：1空军军医大学第一附属医院麻醉与围术期医学科，西安710032；2西安交通大学第二附属医院心血管内科710032

英文单位：1Department of Anesthesia and Perioperative Medicine the First Affiliated Hospital of Air Force Medical University Xi′an 710032 China; 2Department of Cardiovascular Medicine the Second Affiliated Hospital of Xi′an Jiaotong University Xi′an 710032 China

关键词：反复缺血再灌注脑损伤；右美托咪定；NOD样受体蛋白3炎症小体

英文关键词：Repeatedischemia-reperfusionbraininjury;Dexmedetomidine;NOD-likereceptorprotein3inflammasomes

• 摘要：

• 目的 探讨右美托咪定对小鼠反复缺血再灌注（IR）脑损伤时NOD样受体蛋白3（NLRP3）炎症小体表达的影响。方法 选取清洁级健康雄性C57BL/6J小鼠27只作为研究对象，采用随机数字表法分为右美托咪定预先给药组（9只，D组）、IR组（9只）和假手术组（9只，S组）。D组小鼠于建模前30 min腹腔注射25 μg/kg右美托咪定，同期IR组和S组注射等量0.9%氯化钠溶液，30 min后S组小鼠分离出双侧颈总动脉，但不夹闭，D组和IR组经夹闭双侧颈总动脉建立反复IR脑损伤模型。行水迷宫测试并在行为学测试完毕后2 h处死小鼠，取海马组织检测湿/干重比和总含水量；采用聚合酶链反应和蛋白质印迹法检测海马组织中NLRP3、凋亡相关斑点样蛋白（ASC）、半胱氨酸天冬氨酸蛋白酶1（Caspase-1）的mRNA和蛋白表达情况；采用酶联免疫吸附试验法检测海马组织中白细胞介素1β（IL-1β）和IL-18的表达量。结果  IR组逃避潜伏期显著高于D组和S组［（27.6±6.2）s比（15.1±4.6）、（6.8±0.9）s］，且D组逃避潜伏期显著高于S组，而S组穿越原平台次数显著高于D组和IR组［（11.0±2.3）次比（6.7±1.2）、（2.2±0.3）次］，且D组穿越原平台次数显著高于IR组(均P＜0.05)。IR组海马组织湿/干重比及总含水量显著高于D组和S组，且D组海马组织湿/干重比及总含水量显著高于S组(均P＜0.05)。IR组NLRP3、Caspase-1和ASC的mRNA和蛋白表达均显著高于D组和S组，且D组均显著高于S组(均P＜0.05)。IR组海马组织中IL-1β和IL-18表达量均显著高于D组和S组，且D组显著高于S组(均P＜0.05)。结论  IR脑损伤前30 min给小鼠注射右美托咪定，可抑制脑组织NLRP3炎症小体表达，进而减轻脑组织所受损伤。

• Objective To investigate the effect of dexmedetomidine on the expression of NOD-like receptor protein 3 (NLRP3) inflammasomes in mice with repeated ischemia-reperfusion (IR) brain injury. Methods Twenty-seven clean and healthy male C57BL/6J mice were selected. They were divided into dexmedetomidine pre-administration group (9 mice, group D), IR group (9 mice) and sham operation group (9 mice, group S) by random number table method. Mice in group D were given 25μg/kg dexmedetomidine intraperitoneal injection 30 min before modeling. At the same time, mice in IR group and group S were given the same amount of 0.9% sodium chloride solution intraperitoneal injection. After 30 min, mice in group S were isolated bilateral common carotid arteries, but did not clip them. Mice in group D and IR group were clipped bilateral common carotid arteries to establish repeated IR brain injury models. The water maze test was performed and the mice were sacrificed 2 h after the behavioral test. The wet/dry weight ratio and total water content were measured by taking part of hippocampus. The mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteine aspartate specific protease 1 (Caspase-1) in hippocampus were detected by polymerase chain reaction and western blotting. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin-1β (IL-1β) and IL-18 in the hippocampus. Results The escape latency of IR group was significantly higher than that of group D and group S［（27.6±6.2）s vs （15.1±4.6）, （6.8±0.9）s］, and that of group D was significantly higher than that of group S; the number of crossings of the original platform of group S was significantly higher than that of group D and IR group［（11.0±2.3）times vs （6.7±1.2）,（2.2±0.3）times］, and that of group D was significantly higher than that of IR group (all P＜0.05). The wet/dry weight ratio and total water content of hippocampus of IR group were significantly higher than that of group D and group S, and those of group D were significantly higher than those of group S (all P＜0.05). The mRNA and protein expressions of NLRP3, Caspase-1 and ASC of IR group were significantly higher than those of group D and group S, and those of group D were significantly higher than those of group S (all P＜0.05). The expression of IL-1β and IL-18 of IR group was significantly higher than those of group D and group S, and those of group D were significantly higher than those of group S (all P＜0.05). Conclusion  Injecting dexmedetomidine into mice 30 min in advance can inhibit the expression of NLRP3 inflammasomes in brain tissues, thereby reducing the damage to brain tissues.