Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats
Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats
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DOI：
10.1016/s0006-8993(01)02074-1
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发表时间：
2001-03-23
期刊：
影响因子：
2.9
通讯作者：
Devaskar, SU
中科院分区：
文献类型：
--
作者：
Lane, RH;Ramirez, RJ;Devaskar, SU
患有子宫胎盘功能不全和缺氧缺血性损伤的婴儿常表现为脑细胞凋亡。我们的目的是确定子宫胎盘功能不全对脑细胞凋亡相关蛋白Bcl2和Bax基因表达的整体影响，以及它们在增加对低氧诱导的脑细胞凋亡易感性中的作用。因此，我们在足月分娩前2天对妊娠大鼠实施双侧子宫动脉结扎术，造成子宫胎盘功能不全和生长迟缓，并在分娩前3小时将母鼠置于14%FiO(2)中，造成进一步的围产期胎儿缺氧。定量检测大鼠脑组织中Bcl2、Bax基因表达水平及脂质过氧化反应。Caspase-3活性和cAMP在正常缺氧或低氧条件下发育迟缓的足月大鼠中的表达。子宫胎盘功能不全单独引起脑组织Bcl2基因表达水平显著降低，而不改变大脑Bax基因表达水平。丙二醛水平。或caspase-3活性。相反，子宫胎盘功能不全和随后的胎儿缺氧显著增加了脑组织中Bax基因的表达水平，脂质过氧化和caspase-3活性：bcl2基因表达水平持续下降。低氧单独增加大脑cAMP水平，而子宫胎盘功能不全和随后的低氧降低大脑cAMP水平。我们推测，在最初暴露于子宫胎盘功能不全和随后的低氧应激的胎鼠中，Bcl-2基因表达的降低增加了对脑细胞凋亡的易感性。(C)2001 Elsevier Science B.V.保留所有权利。
Infants suffering uteroplacental insufficiency and hypoxic ischemic injury often demonstrate cerebral apoptosis. Our objective was to determine the global effects, of uteroplacental insufficiency upon cerebral gene expression of the apoptosis related proteins Bcl-2 and Bax and their role in increasing vulnerability to hypoxia-induced cerebral apoptosis. We therefore caused uteroplacental insufficiency and growth retardation by performing bilateral uterine: artery ligation upon pregnant rats 2 days prior to term delivery and elicited further perinatal fetal hypoxia by placing maternal rats in 14% FiO(2) 3 h prior to delivery. We quantified cerebral levels of Bcl-2 and Bax mRNA, lipid peroxidation. caspase-3 activity, and cAMP in control and growth retarded term rat pups that experienced either normoxia or hypoxia. Uteroplacental insufficiency alone caused a significant decrease in cerebral Bcl-2 mRNA levels without altering cerebral Bax mRNA levels. malondialdehyde levels. or caspase-3 activity. In contrast, uteroplacental insufficiency and subsequent fetal hypoxia significantly increased cerebral Bax mRNA levels, lipid peroxidation and caspase-3 activity: Bcl-2 mRNA levels continued to be decreased. Hypoxia alone increased cerebral cAMP levels, whereas uteroplacental insufficiency and subsequent hypoxia decreased cerebral cAMP levels. We speculate that the decrease in Bcl-2 gene expression increases the vulnerability towards cerebral apoptosis in fetal rats exposed initially to uteroplacental insufficiency and subsequent hypoxic stress. (C) 2001 Elsevier Science B.V. All rights reserved.