Liao Z B, Zhi X G, Shi Q H, He Z H
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Eur J Neurol. 2008 Feb;15(2):140-9. doi: 10.1111/j.1468-1331.2007.02013.x. Epub 2007 Dec 18.
We explored the regulation of erythropoietin and erythropoietin receptor on traumatic brain injury (TBI), as well as the antiapoptotic effects of recombinant human erythropoietin (rhEPO) treatment. Female Wistar rats were randomly divided into three groups: rhEPO-treated TBI, vehicle-treated TBI, and sham-operated. TBI was induced by the Feeney free falling model. Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of EPO, EPOR and Bcl-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunofluorescence. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL) was used to assess DNA fragmentation after TBI. Induction of EPOR expression persisted for 168 h after TBI, whereas EPO was only slightly elevated for 72 h. In the rhEPO-treated TBI, Bcl-2 mRNA and protein levels were greater than in the vehicle-treated TBI. Bcl-2 mRNA peaked at 24 h and remained stable for 72-120 h. The number of TUNEL-positive cells in the rhEPO-treated TBI was far fewer than in the vehicle-treated TBI. EPOR regulation is enhanced for almost a week after TBI. Administration of rhEPO protects neurons by enhancing Bcl-2 expression, thereby inhibiting TBI-induced neuronal apoptosis.
我们探讨了促红细胞生成素及促红细胞生成素受体在创伤性脑损伤（TBI）中的调控作用，以及重组人促红细胞生成素（rhEPO）治疗的抗凋亡作用。将雌性Wistar大鼠随机分为三组：rhEPO治疗的TBI组、载体治疗的TBI组和假手术组。采用Feeney自由落体模型诱导TBI。在TBI后5、12、24、72、120或168小时处死大鼠。通过逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和免疫荧光法检测EPO、EPOR和Bcl-2的调控情况。采用末端脱氧核苷酸转移酶介导的生物素-dUTP缺口末端标记法（TUNEL）评估TBI后的DNA片段化情况。TBI后EPOR表达的诱导持续168小时，而EPO仅在72小时内略有升高。在rhEPO治疗的TBI组中，Bcl-2 mRNA和蛋白水平高于载体治疗的TBI组。Bcl-2 mRNA在24小时达到峰值，并在72 - 120小时保持稳定。rhEPO治疗的TBI组中TUNEL阳性细胞数量远少于载体治疗的TBI组。TBI后近一周内EPOR调控增强。给予rhEPO可通过增强Bcl-2表达来保护神经元，从而抑制TBI诱导的神经元凋亡。
