Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.
J Neurosurg Anesthesiol. 2012 Jan;24(1):39-50. doi: 10.1097/ANA.0b013e318235af18.
Diabetes mellitus is a metabolic disorder associated with structural and functional alterations of various organ systems including the central nervous system. The aim of present study was to investigate the neuroprotective effect of agmatine (AGM) on cerebral ischemic damage in diabetic rats.
Normoglycemic (n=30) and streptozocine-induced diabetic rats (n=82) were subjected to 30 minutes of suture-occlusion of the middle cerebral artery (MCAO) with 24 or 72 hours of reperfusion. Thirty-nine diabetic rats were treated with AGM (100 mg/kg, intraperitoneal) immediately after 30 minutes of MCAO. To evaluate the motor function, a modified neurological examination and rota-rod exercise were performed. The brain infarct volume and edema volume were assessed. Caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining were used to evaluate cellular apoptosis. Western blot and immunohistochemical analysis were performed to determine the expression of neuronal nitric oxide synthase (NOS) and inducible NOS in ischemic brain tissues.
AGM posttreatment improved the neurobehavioral activity of diabetic MCAO rats at 24 and 72 hours after reperfusion. The infarct size and edema volume were reduced in AGM-treated diabetic rats compared with those in diabetic rats without AGM posttreatment (P<0.01). Immunohistochemical analysis showed that AGM treatment significantly decreased the number of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells in diabetic MCAO rats at 24 and 72 hours after reperfusion (P<0.01). Western blotting and immunohistochemistry results indicated that AGM treatment significantly decreased neuronal NOS and inducible NOS expression in diabetic rats at 24 and 72 hours after reperfusion (all P<0.05).
AGM posttreatment reduced cerebral infarct size and neurological deficit expression in diabetic rats subjected to MCAO. The reduced infarct size was associated with a decrease in apoptosis and NOS expression.
糖尿病是一种代谢紊乱，与包括中枢神经系统在内的各种器官系统的结构和功能改变有关。本研究的目的是探讨胍丁胺（AGM）对糖尿病大鼠脑缺血损伤的神经保护作用。
将正常血糖（n=30）和链脲佐菌素诱导的糖尿病大鼠（n=82）进行 30 分钟大脑中动脉（MCAO）缝线阻塞，再进行 24 或 72 小时再灌注。39 只糖尿病大鼠在 MCAO 后 30 分钟内给予 AGM（100mg/kg，腹腔内）治疗。为了评估运动功能，进行了改良神经检查和转棒运动试验。评估脑梗死体积和水肿体积。用半胱天冬酶-3 活性和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色来评估细胞凋亡。用 Western blot 和免疫组化分析来确定缺血脑组织中神经元型一氧化氮合酶（NOS）和诱导型 NOS 的表达。
AGM 治疗后可改善糖尿病 MCAO 大鼠再灌注后 24 和 72 小时的神经行为活动。与未用 AGM 治疗的糖尿病大鼠相比，AGM 治疗组的梗死面积和水肿体积减小（P<0.01）。免疫组化分析显示，AGM 治疗可显著减少糖尿病 MCAO 大鼠再灌注后 24 和 72 小时的半胱天冬酶-3 阳性和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记阳性细胞数量（P<0.01）。Western blot 和免疫组化结果表明，AGM 治疗可显著降低糖尿病大鼠再灌注后 24 和 72 小时的神经元型 NOS 和诱导型 NOS 表达（均 P<0.05）。
AGM 治疗后可减少糖尿病大鼠 MCAO 后的脑梗死面积和神经功能缺损表达。梗死面积的减少与凋亡和 NOS 表达的减少有关。
