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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (4): 37-42.doi: 10.6040/j.issn.1671-7554.0.2013.709

• 基础医学 • 上一篇    下一篇

丙酮酸钠对新生鼠低血糖脑损伤的神经保护作用

周冬1, 常红2, 孙若鹏1   

  1. 1. 山东大学齐鲁医院儿科, 山东 济南 250012;
    2. 青岛大学附属医院儿科, 山东 青岛 266001
  • 收稿日期:2013-11-25 修回日期:2015-03-10 出版日期:2015-04-10 发布日期:2015-04-10
  • 通讯作者: 周冬.E-mail:zhoudong1106@sohu.com E-mail:zhoudong1106@sohu.com

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

ZHOU Dong1, CHANG Hong2, SUN Ruopeng1   

  1. 1. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong, China
  • Received:2013-11-25 Revised:2015-03-10 Online:2015-04-10 Published:2015-04-10

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摘要： 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 mL和50%葡萄糖0.01 mL+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Morris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.

关键词: 低血糖, 认知功能, 肾病综合征, 膜性肾病, 新生, 神经元, Wistar, 大鼠, 撕脱伤

Abstract: 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 hypodermicly into rats in INS-P group, while dextrose was injected hypodermicly and sodium pyruvate was injected peritoneally 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 neurons 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. Sodium pyruvate administration may be an effective intervention for patients with severe neonatal hypoglycemia to prevent brain injury.

Key words: Rat, Wistar, Neonate, Hypoglycemia, Neurodegeneration, Cognitive function

中图分类号: 

  • R722
[1] Zhou D, Qian J, Liu CX, et al. Repetitive and profound insulin-induced hypoglycemia results in brain damage in newborn rats: An approach to establish an animal model of brain injury induced by neonatal hypoglycemia[J]. Eur J Pediatr, 2008, 167(10): 1169-1174.
[2] 刘振球, 余加林. 早产儿低血糖研究进展[J]. 中国循证儿科杂志, 2008, 3(5): 381-386.
[3] 吴懿. 早产儿血糖测定与胰岛素C肽关系的临床研究[J]. 中国新生儿科杂志, 2008, 23(1): 39-40.
[4] 刘志伟, 陈惠金. 美国新生儿低血糖管理指南[J]. 实用儿科临床杂志, 2010, 25(8): 618-620.
[5] Moro N, Sutton RL. Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat[J]. Exp Neurol, 2010, 225(2): 391-401.
[6] Fukushima M, Lee SM, Moro N, et al. Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury[J]. J Neurotrauma, 2009, 26(7):1095-1110.
[7] Moro N, Ghavim SS, Hovda DA, et al. Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury[J]. Neurosci Lett, 2011, 491(2): 158-162.
[8] Yi JS, Kim TY, Kyu Kim D, et al. Systemic pyruvate administration markedly reduces infarcts and motor deficits in rat models of transient and permanent focal cerebral ischemia[J]. Neurobiol Dis, 2007, 26(1): 94-104.
[9] Pan R, Rong Z, She Y, et al. Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain[J]. Pediatr Res,2012, 72(5): 479-489.
[10] Schmued LC, Hopkins KJ. Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration[J]. Brain Res, 2000, 874(2): 123-130.
[11] D'Amours D, Desnoyers S, D'Silva I, et al. Poly (ADP-ribosyl)ation reactions in the regulation of nuclear functions[J]. Biochem J, 1999, 342 (Pt 2): 249-268.
[12] Ying W, Chen Y, Alano CC, et al. Tricarboxylic acid cycle substrates prevent PARP-mediated death of neurons and astrocytes[J]. J Cereb Blood Flow Metab, 2002, 22(7): 774 -779.
[13] Ha HC, Snyder SH. Poly (ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion[J]. Proc Natl Acad Sci U S A, 1999, 96(24): 13978-13982.
[14] Yu SW, Wang H, Poitras MF, et al. Mediation of poly (ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor[J]. Science, 2002, 297(5579): 259-263.
[15] Ying W, Garnier P, Swanson RA. NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes[J]. Biochem Biophys Res Commun, 2003, 308(4): 809-813.
[16] Ying W, Alano CC, Garnier P, et al. NAD+ as a metabolic link between DNA damage and cell death[J]. J Neurosci Res, 2005, 79(1-2): 216-223.
[17] Suh SW, Aoyama K, Matsumori Y, et al. Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment[J]. Diabetes, 2005, 54(5): 1452-1458.
[18] Lee JY, Kim YH, Koh JY. Protection by pyruvate against transient forebrain ischemia in rats[J]. J Neurosci, 2001, 21(20): RC171.
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