丙酮酸钠对新生鼠低血糖脑损伤的神经保护作用

Neuroprotection of sodium pyruvate on repetitive and profound neonatal hypoglycemic brain injury

目的探讨丙酮酸钠对新生鼠低血糖脑损伤的神经保护作用。方法 36只新生Wistar大鼠随机分为胰岛素处理P组(INS-P组,n=12)、胰岛素+丙酮酸钠处理组(INS-PP组,n=12)和对照组(n=12)。在出生后第2、4、6天分别采用皮下注射胰岛素(15 U/kg)诱导新生鼠低血糖;终止低血糖时INS-P组和INS-PP组分别皮下注射50%葡萄糖0.01 m L和50%葡萄糖0.01 m L+丙酮酸钠500 mg/kg;第3次低血糖处理后1天三组大鼠各取6只取脑组织标本,并采用Fluoro-Jade B(FJB)染色法进行死亡神经元的计数。低血糖损伤6周后,三组各6只大鼠用M orris水迷宫实验检测大鼠的空间学习和记忆能力。结果 INS-PP组与INS-P组相比,变性神经元计数为少,出生后6周INS-PP组大鼠的空间认知能力优于INS-P组,表现在INS-PP组大鼠找到平台的潜伏期短,在池中游泳距离短,在平台所在象限的逗留时间长,穿过平台位置的次数多。结论丙酮酸钠对胰岛素诱导的新生鼠低血糖脑损伤具有保护作用。丙酮酸钠给药可能是防止新生儿低血糖脑损伤的有效干预手段。

Objective To investigate the neuroprotective effect of sodium pyruvate on newborn Wistar rats suffered from repetitive and profound insulin-induced hypoglycemic brain injury.Methods A total of 36 newborn Wistar rats were randomly divided into three groups：insulin-treated P group （INS-P group,n =12）,insulin and sodium pyruvate-treated group （INS-PP group,n =12）,and control group （n =12）.On postnatal day 2,4 and 6,insulin were injected hypodermicly into rats to induce hypoglycemia.After hypoglycemia lasting for 2.5 hours,dextrose was injected hypo-dermicly into rats in INS-P group,while dextrose was injected hypodermicly and sodium pyruvate was injected perito-neally into rats in INS-PP group.On 1 day after the third hypoglycemic insult,the neuronal degeneration in the rats′brains was examined by FJB staining.When the rats were 6 weeks old,their spatial learning and memory ability were detected with Morris’water maze experiment.Results Compared with INS-P group,the number of degenerated neu-rons in INS-PP group reduced and spatial learning and memory ability decreased.For the rats in INS-PP group,the spending time to find the platform was less,swimming distance was shorter,lingering time in the quadrant of platform was longer,and times to cross the platform were increased compared with those in INS-P group.Conclusion Sodium pyruvate can provide a neuroprotective effect on rats suffered from repetitive and profound neonatal hypoglycemia.Sodi-um pyruvate administration may be an effective intervention for patients with severe neonatal hypoglycemia to prevent brain injury.