Kertmen Hayri, Gürer Bora, Yilmaz Erdal Resit, Kanat Mehmet Ali, Arikok Ata Türker, Ergüder Berrin Imge, Hasturk Askin Esen, Ergil Julide, Sekerci Zeki
Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital, Neurosurgery Clinic, Ankara, Turkey.
Ministry of Health, Refik Saydam National Public Health Agency, Ankara, Turkey.
Arch Med Sci. 2015 Oct 12;11(5):1119-28. doi: 10.5114/aoms.2015.54869.
In this study, we tried to determine whether darbepoetin-α would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model.
The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin α), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied.
Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-α increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-α significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-α administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016).
In this study, darbepoetin-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.
在本研究中，我们试图确定在大鼠创伤性脑损伤模型中，达比泊汀-α是否能保护大脑免受氧化应激和细胞凋亡的影响。
将动物随机分为四组；第1组（假手术组），第2组（创伤组），第3组（达比泊汀-α组），第4组（甲基强的松龙组）。假手术组仅进行皮肤切口。在所有其他组中，应用中度创伤性脑损伤模型。
创伤后谷胱甘肽过氧化物酶和超氧化物歧化酶水平均降低（两者p<0.001）；达比泊汀-α增加了两种抗氧化酶的活性（分别为p = 0.001和p<0.001）。创伤导致一氧化氮合酶和黄嘌呤氧化酶水平显著升高（两者p<0.001）。给予达比泊汀-α显著降低了一氧化氮合酶和黄嘌呤氧化酶的水平（两者p<0.001）。此外，创伤导致一氧化氮水平显著升高（p<0.001）；给予达比泊汀-α导致一氧化氮水平在统计学上显著降低（p<0.001）。另一方面，创伤后丙二醛水平升高（p<0.001），达比泊汀-α显著降低了丙二醛水平（p<0.001）。由于损伤后凋亡活性升高，半胱天冬酶-3活性显著增加。达比泊汀-α治疗通过降低半胱天冬酶-3活性显著抑制了细胞凋亡（p<0.001）。在达比泊汀组中，组织病理学评分低于创伤组（p = 0.016）。
在本研究中，达比泊汀-α在保护大脑免受氧化应激、脂质过氧化和细胞凋亡方面至少与甲基强的松龙一样有效。
