Erythropoietin can promote survival of cerebral cells by downregulating Bax gene after traumatic brain injury in rats
Erythropoietin can promote survival of cerebral cells by downregulating Bax gene after traumatic brain injury in rats
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DOI：
10.4103/0028-3886.59466
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发表时间：
2009-11-01
期刊：
影响因子：
2.7
通讯作者：
Wu, M. J.
中科院分区：
文献类型：
--
作者：
Liao, Z. B.;Jiang, G. Y.;Wu, M. J.
背景：创伤性脑损伤（TBI）是成人死亡和发病的重要原因。促红细胞生成素（Epo）可通过上调Bcl-2基因促进脑细胞的存活，但其抗凋亡作用可能是通过对凋亡相关基因表达的差异调节而实现的。目的：本研究探讨Epo作为一种生存因子通过调节Bax的神经保护作用。材料与方法：Wistar大鼠随机分为三组：重组人EPO治疗的（rhEPO）TBI，溶剂治疗的TBI，和假手术。创伤性脑损伤采用Feeney自由落体模型。TBI后5、12、24、72、120或168 h处死大鼠。逆转录-聚合酶链反应（RT-PCR）、免疫印迹和免疫荧光检测Bcl-2的表达。结果：rhEPO处理的大鼠脑中Bax mRNA和蛋白水平低于溶剂处理的大鼠脑。Bax表达的诱导在24小时达到峰值，并保持稳定为72-120小时，在溶剂处理的大鼠脑，而Bax表达的诱导在rhEPO处理的大鼠脑中仅略有升高。TdT介导的dUTP缺口末端标记（TUNEL）阳性细胞的数量在rhEPO处理的大鼠脑中远远少于溶剂处理的大鼠脑。结论：Epo通过抑制TBI诱导的神经元细胞死亡而降低Bax基因表达，从而发挥神经保护作用。
Background: Traumatic brain injury (TBI) is an important cause of adult mortality and morbidity. Erythropoietin (Epo) has been shown to promote the viability of cerebral cells by upregulating Bcl-2 gene; however, Epo may exert its antiapoptotic effect via the differential regulation of the expression of genes involved in the apoptotic process. Aim: The present study examined the neuroprotective effect of Epo as a survival factor through the regulation of the Bax. Materials and Methods: Wistar rats were randomly divided into three groups: Recombinant human EPO treated (rhEPO) TBI, vehicle-treated TBI, and sham-operated. Traumatic brain injury was induced by the Feeney free-falling model. Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of Bcl-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunofluorescence. Results: Bax mRNA and protein levels were lower in the rhEPO)-treated rat brains than in the vehicle-treated rat brains. Induction of Bax expression peaked at 24 h and remained stable for 72-120 h in vehicle-treated rat brains, whereas induction of Bax expression was only slightly elevated in rhEPO-treated rat brains. The number of TdT-mediated dUTP Nick-End Labeling(TUNEL)-positive cells in the rhEPO-treated rat brains was far fewer than in the vehicle-treated rat brains. Conclusions: Epo exerts neuroprotective effect against traumatic brain injury via reducing Bax gene expression involved in inhibiting TBI-induced neuronal cell death.