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目的胰岛素强化治疗增加中度和严重低血糖发生率,严重低血糖诱导的认知障碍的临床报告结果不一致。我们推测存在这样的结论,即反复持续性中度低血糖发作,有利于大脑抵御严重低血糖诱导的损伤。实验方法选九周龄的雄性正常SD大鼠,实验开始的前3天诱导实验组大鼠反复持续性中度低血糖(25～40mg/dl)发作,同时对照组采用生理盐水皮下注射。第4天对全部大鼠采用高胰岛素(0.2units?kg-1?min-1)严重低血糖(约11mg/dl)钳夹试验,持续时间为60分钟或90分钟。之后组织染色采用苏木素伊红染色和Fluoro-JadeB染色以观察神经损伤的程度;行为学测试采用运动和认知测试以评估严重低血糖引起的脑损伤情况。结果严重低血糖可导致大鼠空间学习记忆能力显著降低。反复持续性中度低血糖可预防性保护大鼠大脑,使细胞死亡减少62%～74%,在很大程度上保护了认知功能免受损伤。结论反复持续性中度低血糖在很大程度上限制了后续严重低血糖引起的大脑神经损伤以及相关的认知障碍。总之,反复持续性中度低血糖可以看作是一个适应性的预防性保护,以缓解后续严重低血糖引起的认知障碍。
Intensive insulin therapy aimed at increasing the incidence of moderate and severe hypoglycemia, severe hypoglycemia-induced cognitive impairment clinical findings are inconsistent. We speculate that there is a conclusion that repeated episodes of moderate hypoglycaemia may be beneficial to the brain against severe hypoglycemia-induced damage. Experimental Methods Nine-week-old male normal SD rats were selected. The rats in the experimental group were given repeated episodes of moderate hypoglycemia (25-40 mg / dl) 3 days before the start of the experiment, while the control group was injected subcutaneously with normal saline. On day 4, all rats were subjected to a high-insulin (0.2units? Kg-1? Min-1) severe hypoglycemia (about 11 mg / dl) clamp test for a duration of 60 minutes or 90 minutes. Tissue staining was followed by hematoxylin and eosin staining and Fluoro-JadeB staining to observe the extent of nerve damage; behavioral tests used motor and cognitive tests to assess brain damage following severe hypoglycemia. Severe hypoglycemia results in a significant reduction of spatial learning and memory in rats. Repeated and sustained moderate hypoglycemia can protect rat brain prophylaxis, reducing cell death by 62% -74%, largely protecting cognitive function from injury. Conclusions Repeated persistent mild hypoglycaemia to a large extent limited subsequent serious hypoglycemia-induced brain injury and related cognitive impairment. In summary, repeated persistent mild hypoglycemia can be considered as an adaptive, preventative protection against cognitive disorders caused by subsequent severe hypoglycemia.