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出生后年龄影响低血糖诱导的大鼠脑区多聚(ADP-核糖)聚合酶-1的激活。

Postnatal age influences hypoglycemia-induced poly(ADP-ribose) polymerase-1 activation in the brain regions of rats.

机构信息

Department of Pediatrics, Center for Neurobehavioral Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Pediatr Res. 2009 Dec;66(6):642-7. doi: 10.1203/PDR.0b013e3181bbce69.

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) overactivation plays a significant role in hypoglycemia-induced brain injury in adult rats. To determine the influence of postnatal age on PARP-1 activation, developing and adult male rats were subjected to acute hypoglycemia of equivalent severity and duration. The expression of PARP-1 and its downstream effectors, apoptosis-inducing factor (Aifm1), caspase 3 (Casp3), NF-kappaB (Nfkb1) and bcl-2 (Bcl2), and cellular poly(ADP-ribose) (PAR) polymer expression were assessed in the cerebral cortex, hippocampus, striatum, and hypothalamus at 0 h and 24 h posthypoglycemia. Compared with the control group, PARP-1 expression increased in the cerebral cortex of adult rats 24 h posthypoglycemia, but not at 0 h, and it was accompanied by increased number of PAR-positive cells. The expression was not altered in other brain regions. Aifm1, Nfkb1, Casp3, and Bcl2 expressions also increased in the cerebral cortex of adult rats 24 h posthypoglycemia. Conversely, hypoglycemia did not alter PARP-1 expression and its downstream effectors in any brain region in developing rats. These data parallel the previously demonstrated pattern of hypoglycemia-induced brain injury and suggest that PARP-1 overactivation may determine age- and region-specific vulnerability during hypoglycemia.

摘要

聚(ADP-核糖)聚合酶-1(PARP-1)过度激活在成年大鼠低血糖诱导的脑损伤中起着重要作用。为了确定产后年龄对 PARP-1 激活的影响,发育中和成年雄性大鼠经历了严重程度和持续时间相同的急性低血糖。在低血糖后 0 h 和 24 h 评估大脑皮质、海马体、纹状体和下丘脑的 PARP-1 及其下游效应物,如凋亡诱导因子(Aifm1)、半胱天冬酶 3(Casp3)、核因子 kappaB(Nfkb1)和 bcl-2(Bcl2)的表达,以及细胞多聚(ADP-核糖)(PAR)聚合物的表达。与对照组相比,成年大鼠低血糖后 24 h 大脑皮质的 PARP-1 表达增加,但在 0 h 时没有增加,并且伴随着 PAR 阳性细胞数量的增加。其他脑区的表达没有改变。Aifm1、Nfkb1、Casp3 和 Bcl2 的表达也在成年大鼠低血糖后 24 h 增加。相反,低血糖并未改变发育中大鼠任何脑区的 PARP-1 表达及其下游效应物。这些数据与之前低血糖诱导的脑损伤模式相吻合,表明 PARP-1 过度激活可能决定低血糖期间的年龄和区域特异性易损性。

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