Yang Wan-Chao, Cao Hong-Ling, Wang Yue-Zhen, Li Ting-Ting, Hu Hong-Yu, Wan Qiang, Li Wen-Zhi
Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Department of Anesthesiology, Jilin Province Tumor Hospital, Changchun, Jilin Province, China.
Neural Regen Res. 2021 Aug;16(8):1574-1581. doi: 10.4103/1673-5374.303035.
Studies have shown that hyperglycemia aggravates brain damage by affecting vascular endothelial function. However, the precise mechanism remains unclear. Male Sprague-Dawley rat models of diabetes were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin. Rat models of traumatic brain injury were established using the fluid percussion method. Compared with traumatic brain injury rats without diabetic, diabetic rats with traumatic brain injury exhibited more severe brain injury, manifested as increased brain water content and blood-brain barrier permeability, the upregulation of heme oxygenase-1, myeloperoxidase, and Bax, the downregulation of occludin, zona-occludens 1, and Bcl-2 in the penumbra, and reduced modified neurological severity scores. The intraperitoneal injection of a nitric oxide synthase inhibitor N(5)-(1-iminoethyl)-L-ornithine (10 mg/kg) 15 minutes before brain injury aggravated the injury. These findings suggested that nitric oxide synthase plays an important role in the maintenance of cerebral microcirculation, including anti-inflammatory, anti-oxidative stress, and anti-apoptotic activities in diabetic rats with traumatic brain injury. The experimental protocols were approved by the Institutional Animal Care Committee of Harbin Medical University, China (approval No. ky2017-126) on March 6, 2017.
研究表明，高血糖通过影响血管内皮功能加重脑损伤。然而，确切机制仍不清楚。采用高脂饮食联合腹腔注射链脲佐菌素建立雄性Sprague-Dawley糖尿病大鼠模型。采用液压冲击法建立创伤性脑损伤大鼠模型。与非糖尿病创伤性脑损伤大鼠相比，糖尿病创伤性脑损伤大鼠表现出更严重的脑损伤，表现为脑含水量增加、血脑屏障通透性增加、血红素加氧酶-1、髓过氧化物酶和Bax上调、半暗带中闭合蛋白、紧密连接蛋白1和Bcl-2下调，以及改良神经功能缺损评分降低。脑损伤前15分钟腹腔注射一氧化氮合酶抑制剂N(5)-(1-亚氨基乙基)-L-鸟氨酸（10 mg/kg）会加重损伤。这些发现表明，一氧化氮合酶在维持脑微循环中起重要作用，包括在糖尿病创伤性脑损伤大鼠中的抗炎、抗氧化应激和抗凋亡活性。实验方案于2017年3月6日获得中国哈尔滨医科大学实验动物护理委员会批准（批准号ky2017-126）。
