Huang Yu-Hua, Chung Chia-Li, Tsai Hung-Pei, Wu Shu-Chuan, Chang Chih-Zen, Chai Chee-Yin, Lee Tao-Chen, Kwan Aij-Lie
Graduate Institute of Medicine, Col-lege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Depart-ment of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Neurosurgery. 2017 May 1;80(5):809-815. doi: 10.1093/neuros/nyx016.
Hyperglycemia is common and showed to be risky for poor prognosis in patients with subarachnoid hemorrhage (SAH). However, the causality and mechanism underlying this observation are not well established.
To investigate the relationship between hyperglycemia and cerebral vasospasm with its pathogenesis in a rat model of SAH.
One-shot SAH model was employed in male Sprague-Dawley rats. Hyperglycemia was triggered by intraperitoneal streptozotocin administration (50 mg/kg) 7 days before SAH induction. The severity of cerebral vasospasm was determined by the cross-sectional area of basilar artery (BA) in male rats randomly assigned to 1 of 4 groups: control, hyperglycemia only, SAH only, and SAH with hyperglycemia. The expression of endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in the BA were analyzed by immunohistochemistry.
The mean (standard deviation) blood glucose level was 433.0 (98.3) and 156.5 (31.7) mg/dL in streptozotocin -treated and untreated rats, respectively. Hyperglycemic rats exhibited poorer neurobehavioral performance than normoglycemic rats when subjected to SAH. Hyperglycemia-mediated exacerbation of vasospasm was evident by the greater decrease in the BA cross-sectional area in the hyperglycemic SAH group than in the SAH only group. Furthermore, there was more decreased expression of eNOS and increased expression of iNOS within the vessels of the hyperglycemic SAH rats.
Hyperglycemia exacerbated cerebral vasospasm and was associated with poorer neurological outcomes following SAH. Our findings also suggested the nitric oxide pathway as a potential underlying mechanism via the dysregulation of eNOS and iNOS.
高血糖在蛛网膜下腔出血（SAH）患者中很常见，且已显示对预后不良具有风险。然而，这一观察结果背后的因果关系和机制尚未完全明确。
在SAH大鼠模型中研究高血糖与脑血管痉挛之间的关系及其发病机制。
采用一次性SAH模型，用于雄性Sprague-Dawley大鼠。在SAH诱导前7天，通过腹腔注射链脲佐菌素（50 mg/kg）引发高血糖。将雄性大鼠随机分为4组中的1组：对照组、仅高血糖组、仅SAH组和高血糖合并SAH组，通过基底动脉（BA）的横截面积来确定脑血管痉挛的严重程度。采用免疫组织化学法分析BA中内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）的表达。
链脲佐菌素处理组和未处理组大鼠的平均（标准差）血糖水平分别为433.0（98.3）和156.5（31.7）mg/dL。SAH时，高血糖大鼠的神经行为表现比血糖正常的大鼠差。高血糖SAH组BA横截面积的减小幅度大于仅SAH组，表明高血糖介导的血管痉挛加剧。此外，高血糖SAH大鼠血管内eNOS表达的降低和iNOS表达的增加更为明显。
高血糖加剧了SAH后的脑血管痉挛，并与较差的神经学预后相关。我们的研究结果还表明，一氧化氮途径可能是通过eNOS和iNOS的失调作为潜在的潜在机制。
