Cho Eun-Hwa, Seo Eun-Hye, Hong Seung-Wan, Kim Seong-Hyop
Department of Infection and Immunology, Konkuk University School of Medicine, Seoul 05029, Republic of Korea.
BK21 Plus, Department of Cellular and Molecular Medicine, Konkuk University School of Medicine, Seoul 05029, Republic of Korea.
Int J Mol Sci. 2024 Nov 21;25(23):12505. doi: 10.3390/ijms252312505.
This study evaluated the effect of ulinastatin on blood-brain barrier (BBB) dysfunction in rats with postoperative cognitive dysfunction (POCD) following general anaesthesia with isoflurane. Specifically, we examined BBB permeability and the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Rats in the ulinastatin group received the drug intraperitoneally (50,000 U/mL), while controls received normal saline (1 mL) administered before general anaesthesia. Isoflurane (1.5% volume) anaesthesia was induced for 2 h. Cognitive function was assessed using the Y-maze test. Two days after anaesthesia, BBB permeability was measured using Evans blue, and TIMP-1 expression was evaluated. Both groups experienced cognitive decline following anaesthesia. However, the ulinastatin group showed a more limited decrease (control group, 64.2 ± 19.3 → 30.2 ± 16.2, = 0.008; ulinastatin group, 70.0 ± 15.7 → 66.5 ± 12.0, = 0.67). The ulinastatin group showed a significantly lower permeability of the BBB (0.034 ± 0.003 µg/g in control group vs. 0.005 ± 0.002 µg/g in ulinastatin group, = 0.0001), and also showed a significantly higher value of TIMP-1 expression (5.81 ± 1.94% in control group vs. 13.97 ± 2.59% in ulinastatin group, = 0.0001). Administration of ulinastatin before general anaesthesia mitigated cognitive decline in rats with POCD, likely through the prevention of BBB dysfunction, as evidenced by the lower BBB permeability and increased TIMP-1 expression.
本研究评估了乌司他丁对异氟烷全身麻醉后发生术后认知功能障碍（POCD）的大鼠血脑屏障（BBB）功能障碍的影响。具体而言，我们检测了BBB通透性以及基质金属蛋白酶组织抑制因子-1（TIMP-1）的表达。乌司他丁组大鼠腹腔注射该药物（50,000 U/mL），而对照组在全身麻醉前给予生理盐水（1 mL）。采用1.5%体积分数的异氟烷诱导麻醉2小时。使用Y迷宫试验评估认知功能。麻醉后两天，用伊文思蓝测量BBB通透性，并评估TIMP-1表达。两组在麻醉后均出现认知功能下降。然而，乌司他丁组的下降幅度较小（对照组，64.2±19.3→30.2±16.2，P = 0.008；乌司他丁组，70.0±15.7→66.5±12.0，P = 0.67）。乌司他丁组的BBB通透性显著更低（对照组为0.034±0.003 μg/g，乌司他丁组为0.005±0.002 μg/g，P = 0.0001），并且TIMP-1表达值也显著更高（对照组为5.81±1.94%，乌司他丁组为13.97±2.59%，P = 0.0001）。在全身麻醉前给予乌司他丁可减轻POCD大鼠的认知功能下降，这可能是通过预防BBB功能障碍实现的，较低的BBB通透性和增加的TIMP-1表达证明了这一点。
