Chang Y S, Park W S, Lee M, Kim K S, Shin S M, Choi J H
Department of Pediatrics, Samsung Medical Center, Sung Kyun Kwan University College of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 130-230, South Korea.
Brain Res. 1998 Jul 6;798(1-2):271-80. doi: 10.1016/s0006-8993(98)00470-3.
The purpose of this study was to test the hypothesis that hyperglycemia ameliorates changes in brain cell membrane function and preserves cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. A total of 42 ventilated piglets were divided into 4 groups, normoglycemic/normoxic(group 1, n=9), hyperglycemic/normoxic(group 2, n=8), normoglycemic/hypoxic-ischemic(group 3, n=13) and hyperglycemic/hypoxic-ischemic(group 4, n=12) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Hyperglycemia (blood glucose 350-400 mg/dl) was maintained for 90 min before and throughout hypoxia-ischemia using modified glucose clamp technique. Changes in cytochrome aa3 were continuously monitored using near infrared spectroscopy. Blood and CSF glucose and lactate were monitored. Na+, K+-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia-ischemia, glucose levels in blood and CSF were significantly elevated in hyperglycemic/hypoxic-ischemic group compared with normoglycemic/hypoxic-ischemic group, but lactate levels in blood and CSF were not different between two groups. At the end of hypoxia-ischemia of group 3 and 4, triangle up Cyt aa3, Na+, K+-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups 1 and 2, but were not different between groups 3 and 4. Levels of conjugated dienes and brain lactate were significantly increased in groups 3 and 4 compared with groups 1 and 2, and were significantly elevated in group 4 than in group 3 (0.30+/-0.11 vs. 0.09+/-0.02 micromol g-1 protein, 26.4+/-7.6 vs. 13.1+/-2.6 mmol kg-1, p<0.05). These findings suggest that hyperglycemia does not reduce the changes in brain cell membrane function and does not preserve cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. We speculate that hyperglycemia may be harmful during hypoxia-ischemia due to increased levels of lipid peroxidation in newborn piglet.
在新生仔猪缺氧缺血期间，高血糖可改善脑细胞膜功能变化并维持脑内高能磷酸盐水平。总共42只接受通气的仔猪被分为4组，即正常血糖/正常氧合组（第1组，n = 9）、高血糖/正常氧合组（第2组，n = 8）、正常血糖/缺氧缺血组（第3组，n = 13）和高血糖/缺氧缺血组（第4组，n = 12）。通过结扎双侧颈总动脉并同时吸入8%氧气30分钟诱导脑缺氧缺血。在缺氧缺血前及整个过程中，使用改良的葡萄糖钳夹技术将血糖维持在350 - 400mg/dl的高血糖水平90分钟。使用近红外光谱连续监测细胞色素aa3的变化。监测血液和脑脊液中的葡萄糖及乳酸水平。通过生化方法测定大脑皮质中的Na + 、K + -ATP酶活性、脂质过氧化产物（共轭二烯）、组织高能磷酸盐（ATP和磷酸肌酸）水平以及脑葡萄糖和乳酸水平。在缺氧缺血期间，与正常血糖/缺氧缺血组相比，高血糖/缺氧缺血组血液和脑脊液中的葡萄糖水平显著升高，但两组血液和脑脊液中的乳酸水平无差异。在第3组和第4组缺氧缺血结束时，与正常氧合的第1组和第2组相比，脑内细胞色素aa3的正向三角波、Na + 、K + -ATP酶活性、ATP和磷酸肌酸值显著降低，但第3组和第4组之间无差异。与第1组和第2组相比，第3组和第4组中的共轭二烯水平和脑乳酸水平显著升高，且第4组显著高于第3组（0.30±0.11对0.09±0.02μmol g -1 蛋白质，26.4±7.6对13.1±2.6mmol kg -1 ，p < 0.05）。这些发现表明，在新生仔猪缺氧缺血期间，高血糖并不能减轻脑细胞膜功能的变化，也不能维持脑内高能磷酸盐水平。我们推测，由于新生仔猪脂质过氧化水平升高，高血糖在缺氧缺血期间可能是有害的。
