高血糖（糖尿病）是脑缺血后出血的重要诱导因素。本研究利用大鼠模型检测了氢气对这类损伤的作用。72只SD大鼠分成4组，假手术组、脑缺血组、脑缺血治疗组。所有动物脑缺血模型制备后15分钟注射50%葡萄糖(6 ml/kg i.p.)。90分钟缺血后开始再灌注并同时呼吸氢气2小时。注射50%葡萄糖后0 h, 0.5 h, 4 h, 和 6 h后分别检测血糖水平，缺血后24小时后分别测定缺血和出血体积、神经行为学评分、氧化应激（8OH-dG、HNE和nitrotyrosine分别代表核酸、脂肪和蛋白氧化损伤指标）、MMP9和2活性。结果发现，呼吸氢气能有效降低缺血和出血体积，提高神经行为学评分，效应与氧化应激MMP9和2活性的降低有关系。特别是发现在注射50%葡萄糖后4 h（就是在呼吸氢气2小时结束后45分钟），血糖从500降低到366 mg/dl，但治疗对ZO-1, occluding, collagen IV or aquaporin4的表达没有影响（这说明什么？应该好好分析一下）。该研究说明呼吸氢气确实能对高血糖增强脑出血诱发的脑出血损伤有保护作用，但在氧化应激和血糖水平方面的具体机制需要深入研究。

 

HYDROGEN GAS REDUCED ACUTE HYPERGLYCEMIA-ENHANCED

HEMORRHAGIC TRANSFORMATION IN A FOCAL ISCHEMIA RAT MODEL

C. H. CHEN,a,b M. ANATOL,a Y. ZHAN,a,c W. W. LIU,a R. P. OSTROWKI,a J. TANGa AND J. H. ZHANGa,d,e*

aDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

bDepartment of Anatomy and Embryology, Peking University Health Science Center, Beijing, PR China

cDepartment of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China

dDepartment of Neurosurgery, Loma Linda University, Loma Linda, CA, USA

eDepartment of Anesthesiology, Loma Linda University, Loma Linda, CA, USA

Neuroscience xx (2010) xxx

Abstract—Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague–Dawley rats (n_72) were divided into the following groups: sham; sham treated with hydrogen gas (H2); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H2 (MCAO_H2). All the rats received an injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 h during reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluating by the level of 8 Hydroxyguanosine  (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after ischemia. We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen is accompanied by a reduction of the expressions of 8OHG, HNE, nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500_32.51 to 366_68.22 mg/dl at 4 h after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occluding, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced the infarction, hemorrhagic transformation, and improved neurological functions in rat. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation. © 2010 Published by Elsevier Ltd on behalf of IBRO.

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