Asialoerythropoietin attenuates neuronal cell death in the hippocampal CA1 region after transient forebrain ischemia in a gerbil model
Asialoerythropoietin attenuates neuronal cell death in the hippocampal CA1 region after transient forebrain ischemia in a gerbil model
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亚洲促红细胞生成素可减轻沙鼠模型短暂前脑缺血后海马 CA1 区神经元细胞死亡
DOI：
10.1179/016164110x12700393823336
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发表时间：
2010
影响因子：
1.9
通讯作者：
T. Kuroiwa
中科院分区：
文献类型：
--
作者：
T. Yamashita;N. Nonoguchi;T. Ikemoto;S. Miyatake;T. Kuroiwa
摘要 背景与目的：全身给予高剂量重组人促红细胞生成素（rhEPO）可减轻缺血性损伤。然而，大剂量rhEPO由于其促红细胞生成作用，可能会增加血液粘度，从而加重缺血性病变。 Asialoerythropoietin (asialoEPO) 是一种 EPO 衍生物，血浆半衰期极短，其促红细胞生成作用比天然 EPO 低得多。我们试图确定 asialoEPO 在沙鼠短暂前脑缺血模型中是否发挥与天然 EPO 相同的神经保护作用。方法：对 23 只成年沙鼠进行了双侧颈总动脉的短暂闭塞。腹腔内注射药物（asialoEPO或rhEPO，10 U/g体重）或磷酸盐缓冲盐水（PBS）3次（缺血性损伤前3小时、缺血性损伤后立即和24小时后）。分别在第 6 天和第 7 天进行学习和记忆测试，并在第 7 天进行组织学分析。 结果：与 PBS 治疗的动物相比，用 asialoEPO 和 rhEPO 治疗的动物显示出显着的神经功能改善。 rhEPO处理的动物（103.57±27.90个细胞/mm3）和asialoEPO处理的（144.99±34.87个细胞/mm3）动物的CA1区中存活神经元的数量高于PBS处理的动物（19.53±3.79个细胞/mm3）。 rhEPO处理的动物（33.40±8.13细胞/mm3）和asialoEPO处理的动物（29.28±14.91细胞/mm3）中末端二核苷酸转移酶介导的UTP末端标记阳性细胞显着低于PBS处理的动物（76.67±8.14细胞/mm3）。 AsialoEPO 治疗对红细胞生成没有任何影响。结论：多次给药asialoEPO与EPO一样，可以保护海马CA1神经元免受缺血性损伤，而不影响红细胞生成。
Abstract Background and purpose: Systemic administration of high-dose recombinant human erythropoietin (rhEPO) is known to attenuate ischemic injury. However, high-dose rhEPO might aggravate ischemic lesions by increasing blood viscosity because of its erythropoietic effects. Asialoerythropoietin (asialoEPO), an EPO derivative with an extremely short plasma half-life, has considerably lesser erythropoietic effect than that of naive EPO. We attempted to determine whether asialoEPO exerts the same neuroprotective effect as naive EPO in a gerbil transient forebrain ischemia model. Methods: Transient occlusion of both the common carotid arteries was performed in 23 adult gerbils. The drugs (asialoEPO or rhEPO, 10 U/g bodyweight) or phosphate-buffered saline (PBS) were injected intraperitoneally at three times (3 hours before, immediately after, and 24 hours after the ischemic insult). Learning and retention tests were performed on days 6 and 7, respectively, and histological analyses were performed on day 7. Results: Animals treated with asialoEPO and rhEPO showed significant neurological improvement compared to the PBS-treated animals. The number of viable neurons in the CA1 field of the rhEPO-treated (103.57 ± 27.90 cells/mm) and asialoEPO-treated (144.99 ± 34.87 cells/mm) animals was higher than that of the PBS-treated animals (19.53 ± 3.79 cells/mm). Terminal dinucleotidyltransferase-mediated UTP end labeling-positive cells were significantly lower in the rhEPO-treated (33.40 ± 8.13 cells/mm) and asialoEPO-treated (29.28 ± 14.91 cells/mm) animals than in the PBS-treated animals (76.67 ± 8.14 cells/mm). AsialoEPO treatment did not have any effect on erythropoiesis. Conclusion: Multiple dosing of asialoEPO, like EPO, could protect the hippocampal CA1 neurons from ischemic damage without affecting erythropoiesis.