中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (8): 1574-1581.doi: 10.4103/1673-5374.303035

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

抑制一氧化氮合酶可加重糖尿病合并创伤性脑损伤大鼠的脑损伤程度

  

  • 出版日期:2021-08-15 发布日期:2021-01-13
  • 基金资助:

    中国国家自然科学项目(81400989

Inhibition of nitric oxide synthase aggravates brain injury in diabetic rats with traumatic brain injury

Wan-Chao Yang1, #, Hong-Ling Cao2, #, Yue-Zhen Wang1, Ting-Ting Li1, Hong-Yu Hu1, Qiang Wan1, Wen-Zhi Li1,*   

  1. 1Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China; 2Department of Anesthesiology, Jilin Province Tumor Hospital, Changchun, Jilin Province, China
  • Online:2021-08-15 Published:2021-01-13
  • Contact: Wen-Zhi Li, MD, Wenzhili9@126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81400989 (to WCY).

摘要:

高血糖可通过影响血管内皮功能来加重脑部损伤,但其具体的作用机制尚不清楚。实验通过高糖高脂饮食以及腹腔注射链脲佐菌素诱导建立雄性SD大鼠糖尿病模型,以流体压力损伤法建立创伤性脑损伤模型。结果显示,与单纯脑损伤大鼠相比,合并糖尿病的脑损伤大鼠表现出更严重的脑损伤,其脑含水量更高,血脑屏障通透性更强,损伤半暗带中血红素加氧酶1、髓过氧化物酶和Bax表达上调,occludin,ZO-1和Bcl-2表达下调,且改良神经功能评分较低。而在脑损伤前15min腹腔注射一氧化氮合酶抑制剂L-亚氨基乙基鸟氨酸(10mg/kg)可加剧上述损伤。表明一氧化氮合酶在维持糖尿病合并创伤性脑损伤中脑微循环、抗炎、抗氧化、抗细胞凋亡等方面发挥重要作用,且抑制一氧化氮合酶会加重糖尿病大鼠的脑损伤。实验于2017年3月6日经哈尔滨医科大学机构动物伦理委员会批准(批准号ky2017-126)。

https://orcid.org/0000-0003-4196-524X (Wen-Zhi Li)

关键词: 一氧化氮合酶, 创伤性脑损伤, 糖尿病, 神经功能, 血脑屏障, 细胞凋亡, 炎症, 脑水肿, 损伤

Abstract: 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.

Key words: apoptosis, blood-brain barrier, brain edema, diabetes mellitus, inflammation, injury, neurological function, nitric oxide synthase, traumatic brain injury