反复低血糖加剧糖尿病脑缺血性损伤

作者：陈晓婷译 来源：医学论坛网

　　美国的一项研究显示，线粒体释放自由基增加可能会加剧经胰岛素治疗的链脲霉素诱导糖尿病（insulin- treatedstreptozotocin-diabetic, ITD）+反复低血糖（RH）大鼠脑缺血性损伤。因此，RH可能是一个未被发现但非常重要的加剧糖尿病脑缺血性损伤的因素。这是对RH加剧糖尿病动物脑缺血性损伤研究的第一次报告。研究报告2011年3月31日在线发表于美国《卒中》（Stroke）杂志。

　　卒中和心脏病是糖尿病最严重的并发症，占到糖尿病死亡率的65％以上。虽然强化胰岛素治疗大大改善了糖尿病及其并发症的预后，但它却是RH的高危因素。研究者旨在通过啮齿动物糖尿病模型，检验RH加剧脑缺血性损伤的假设。在对照组和链脲霉素诱导糖尿病大鼠全脑缺血后，研究者鉴定海马CA1区神经元的死亡程度。糖尿病动物又包括ITD组大鼠和发作10次低血糖的ITD组大鼠（ITD+RH）；一天两次诱导低血糖（血糖55—65mg/dL），连续 5天。

　　结果显示，与对照组相比，不加控制的糖尿病（伴链脲霉素诱导的糖尿病、且未经治疗的动物）缺血性损伤增加70％。与糖尿病组相比，胰岛素治疗能降低64％的缺血性损害。然而，与ITD组相比，ITD+RH大鼠增加超过44％的损伤。研究者还注意到，ITD+RH大鼠线粒体释放自由基增加。 

　　相关链接：Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Streptozotocin-Induced Diabetic Rats

    原文摘要:

Background and Purpose—Stroke and heart disease are the most serious complications of diabetes accounting for >65% of mortality among diabetics. Although intensive insulin therapy has significantly improved the prognosis of diabetes and its complications, it is associated with an elevated risk of recurrent hypoglycemia (RH). We tested the hypothesis that RH exacerbates cerebral ischemic damage in a rodent model of diabetes.

Method—We determined the extent of neuronal death in CA1 hippocampus after global cerebral ischemia in control and streptozotocin-induced diabetic rats. Diabetic animals included an insulin-treated streptozotocin-diabetic (ITD) group and a group of ITD rats exposed also to 10 episodes of hypoglycemia (ITD+recurrent hypoglycemia: RH). Hypoglycemia (55 to 65 mg/dL blood glucose) was induced twice daily for 5 consecutive days.

Results—As expected, uncontrolled diabetes (streptozotocin-diabetes, untreated animals) resulted in a 70% increase in ischemic damage as compared with the control group. Insulin treatment was able to lower ischemic damage by 64% as compared with the diabetic group. However, ITD+RH rats had 44% more damage when compared with the ITD group. We also observed that free radical release from mitochondria is increased in ITD+RH rats.

Conclusions—This is the first report on the impact of RH in exacerbating cerebral ischemic damage in diabetic animals. Our results suggest that increased free radical release from mitochondria may be responsible for observed increased ischemic damage in ITD+RH rats. RH thus may be an unexplored but important factor responsible for increased ischemic damage in diabetes.