Kim Young Sung, Sohn Sung-Hwa, Min Too Jae
Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
Neuromolecular Med. 2023 Mar;25(1):136-143. doi: 10.1007/s12017-022-08721-2. Epub 2022 Aug 2.
Ulinastatin (UTI) has neuroprotective properties. Neurologic insults, including hypoxia and use of anesthetic agents, cause postoperative cognitive dysfunction and alter gamma-aminobutyric acid (GABA) function. This study aimed to assess whether UTI could preserve learning and memory using a zebrafish hypoxic behavior model and biomarkers. Zebrafish (6-8 months of age and 2.5-3.5 cm long) were divided into eight groups as follows: phosphate-buffered saline (PBS) control, hypoxia + PBS, UTI (10,000, 50,000, and 100,000 units/kg), and hypoxia with UTI (10,000, 50,000, and 100,000 units/kg) groups. The endpoints of the T-maze experiment included total time, distance moved, and frequency in target or opposite compartment. We also measured the degree of brain infarction using 2,3,5‑triphenyltetrazolium chloride staining, assessed SA-β-galactosidase activity, and examined GABA receptor expression using real-time polymerase chain reaction. In a dose-dependent manner, UTI affected learning and memory in zebrafish. Despite hypoxia, 100,000 units/kg of UTI preserved preference (time and distance) for the target compartment. More than 50,000 units/kg of UTI also showed reduced hypoxia-induced brain infarction, decreased SA-β-galactosidase levels, and upregulated GABA receptors. This study demonstrated that the location of the GABA receptor is affected by hypoxia or UTI.
乌司他丁（UTI）具有神经保护特性。包括缺氧和使用麻醉剂在内的神经损伤会导致术后认知功能障碍，并改变γ-氨基丁酸（GABA）功能。本研究旨在使用斑马鱼缺氧行为模型和生物标志物评估UTI是否能保护学习和记忆。将6至8月龄、体长2.5至3.5厘米的斑马鱼分为八组，如下：磷酸盐缓冲盐水（PBS）对照组、缺氧+PBS组、UTI（10000、50000和100000单位/千克）组，以及缺氧+UTI（10000、50000和100000单位/千克）组。T迷宫实验的终点包括总时间、移动距离以及在目标或对侧隔室的频率。我们还使用2,3,5-三苯基氯化四氮唑染色测量脑梗死程度，评估SA-β-半乳糖苷酶活性，并使用实时聚合酶链反应检测GABA受体表达。UTI以剂量依赖的方式影响斑马鱼的学习和记忆。尽管存在缺氧情况，但100000单位/千克的UTI保留了对目标隔室的偏好（时间和距离）。超过50000单位/千克的UTI还显示出缺氧诱导的脑梗死减少、SA-β-半乳糖苷酶水平降低以及GABA受体上调。本研究表明，GABA受体的定位受缺氧或UTI的影响。
