Lanier W L, Hofer R E, Gallagher W J
Department of Anesthesiology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota 55905, USA.
Anesthesiology. 1996 Apr;84(4):917-25. doi: 10.1097/00000542-199604000-00020.
Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome.
Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques.
Before ischemia, D rats had greater concentrations of brain glucose (12.18 +/- 2.67 micromol/g) than did either ID (5.10 +/- 1.33) or ND (3.20 +/- 0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/- 0.28) than in either ID (0.29 +/- 0.09) or ND (0.36 +/- 0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups.
These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic-but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.
糖尿病相关的高血糖会加重全脑缺血后的神经损伤。在前脑缺血（双侧颈动脉闭塞加低血压10分钟）大鼠模型的研究中发现，给糖尿病大鼠输注胰岛素使其血糖急性恢复正常，其神经功能结局与非糖尿病的血糖正常大鼠相似。本研究评估了脑葡萄糖、糖原、乳酸和高能磷酸酯浓度，以确定可能解释缺血后结局改变的代谢相关性。
54只戊巴比妥麻醉的Sprague-Dawley大鼠被分为三组：慢性高血糖糖尿病大鼠（D组；n = 18）；胰岛素治疗的急性血糖正常糖尿病大鼠（ID组；n = 18）；非糖尿病大鼠（ND组；n = 18）。这些组进一步分为每组6只大鼠的亚组，分别接受无缺血、持续10分钟无前再灌注的前脑缺血或缺血加15分钟再灌注。原位冷冻后切除大脑，使用酶荧光技术测量代谢物。
缺血前，D组大鼠脑葡萄糖浓度（12.18±2.67微摩尔/克）高于ID组（5.10±1.33）和ND组（3.20±0.27）（P < 0.05）。所有组缺血前脑糖原相似。缺血结束时，D组脑乳酸浓度比ID组高86%，比ND组高61%（P < 0.05），反映出D组缺血时葡萄糖加糖原的消耗量更高（P < 0.05）。通过腺苷酸池能荷评估的高能磷酸酯浓度，在D组（能荷 = 0.60±0.28）比ID组（0.29±0.09）和ND组（0.36±0.07；P < 0.05）保存得更好。再灌注15分钟后，所有组的能荷恢复到缺血前水平（即0.91 - 0.92）。
这些研究表明，D组大鼠缺血时碳水化合物消耗量和乳酸生成量比ID组或ND组大鼠更多。在这些条件下，D组大鼠缺血时而非缺血后的能量状态更好。ID组大鼠的急性胰岛素治疗导致其代谢特征与ND组大鼠相似。这些结果表明，在该模型中，缺血期间的原发性能量衰竭不是高血糖糖尿病大鼠损伤更严重的原因，急性胰岛素治疗后结局改善也不是能量增强的原因。
