胰岛素诱导的血糖正常可改善高血糖大鼠的缺血结局。

Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats.

作者信息

Warner D S, Gionet T X, Todd M M, McAllister A M

机构信息

Department of Anesthesia, University of Iowa, Iowa City 52242.

出版信息

Stroke. 1992 Dec;23(12):1775-80; discussion 1781. doi: 10.1161/01.str.23.12.1775.

DOI:10.1161/01.str.23.12.1775

PMID:1448829

Abstract

BACKGROUND AND PURPOSE

Hyperglycemia is known to aggravate ischemic brain damage. This study sought to determine if preischemic insulin-induced normoglycemia would improve outcome in hyperglycemic rats.

METHODS

Normal rats and rats with 5-7 days of streptozotocin-induced diabetes were studied. Normal rats served as either fasted normoglycemic controls or dextrose-infused (hyperglycemic) controls. In the acutely diabetic rats either no insulin was given or insulin was given at 30 or 90 minutes before ischemia so as to induce preischemic normoglycemia. All rats underwent 10 minutes of forebrain ischemia. After 5 days of recovery, motor function and histological outcome were assessed.

RESULTS

Untreated diabetic rats and dextrose-infused control rats had greater hippocampal CA1 damage than normoglycemic control rats. In contrast, insulin-treated diabetic rats had less hippocampal CA1 damage than either untreated diabetic rats or dextrose-infused control rats. Injury in the two insulin-treated groups was not significantly different from that in the normoglycemic control group (all three groups had plasma glucose values of 120-150 mg/dl immediately prior to ischemia). Despite similar plasma glucose values (300-400 mg/dl), fewer postischemic seizures (0% versus 67%) were observed in the untreated diabetic group than in the dextrose-infused control group (p < 0.001).

CONCLUSIONS

Hyperglycemia caused by either dextrose infusion or streptozotocin-induced diabetes resulted in exacerbated ischemic brain damage. Insulin therapy to rapidly induce preischemic normoglycemia improved outcome from forebrain ischemia in the acutely diabetic rats. Glucose-infused hyperglycemic rats frequently exhibited postischemic generalized seizures while acutely diabetic rats did not. The latter results implicate some adaptive/protective mechanism associated with acute streptozotocin-induced diabetes that results in a decreased sensitivity to hyperglycemia-augmented ischemic brain damage.

摘要

背景与目的

已知高血糖会加重缺血性脑损伤。本研究旨在确定缺血前胰岛素诱导的血糖正常是否会改善高血糖大鼠的预后。

方法

对正常大鼠和经链脲佐菌素诱导糖尿病5 - 7天的大鼠进行研究。正常大鼠作为禁食血糖正常对照组或输注葡萄糖（高血糖）对照组。在急性糖尿病大鼠中，要么不给胰岛素，要么在缺血前30或90分钟给予胰岛素以诱导缺血前血糖正常。所有大鼠均经历10分钟的前脑缺血。恢复5天后，评估运动功能和组织学结果。

结果

未治疗的糖尿病大鼠和输注葡萄糖的对照大鼠比血糖正常的对照大鼠有更严重的海马CA1区损伤。相比之下，胰岛素治疗的糖尿病大鼠比未治疗的糖尿病大鼠或输注葡萄糖的对照大鼠海马CA1区损伤更少。两个胰岛素治疗组的损伤与血糖正常对照组无显著差异（所有三组在缺血前即刻血糖值均为120 - 150mg/dl）。尽管血糖值相似（300 - 400mg/dl），但未治疗的糖尿病组缺血后癫痫发作的发生率（0%）低于输注葡萄糖的对照组（67%）（p < 0.001）。

结论

输注葡萄糖或链脲佐菌素诱导的糖尿病所致的高血糖会导致缺血性脑损伤加重。胰岛素治疗迅速诱导缺血前血糖正常可改善急性糖尿病大鼠前脑缺血的预后。输注葡萄糖的高血糖大鼠经常出现缺血后全身性癫痫发作，而急性糖尿病大鼠则不然。后一结果提示与急性链脲佐菌素诱导的糖尿病相关的一些适应性/保护机制，该机制导致对高血糖加重的缺血性脑损伤的敏感性降低。