Kertmen Hayri, Celikoglu Erhan, Ozturk Ozden Caglar, Gürer Bora, Bozkurt Huseyin, Kanat Mehmet Ali, Arikok Ata Turker, Erguder Berrin Imge, Sargon Mustafa Fevzi, Sekerci Zeki
Neurosurgery Clinic, Diskapi Yildirim Beyazit Education and Research Hospital, Ministry of Health, Ankara, Turkey.
Neurosurgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, Ministry of Health, Istanbul, Turkey.
Arch Med Sci. 2018 Oct;14(6):1459-1470. doi: 10.5114/aoms.2017.65650. Epub 2017 Jan 31.
Tetracosactide is an engineered peptide that applies the same biological impacts as the endogenous adrenocorticotropic hormone. Previous studies indicated that tetracosactide has anti-inflammatory, antioxidant and neurotrophic activity. In this study, we hypothesized that tetracosactide may have protective effects in spinal cord ischemia-reperfusion injury.
Rabbits were randomized into the accompanying four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (tetracosactide). In the control group, just a laparotomy was performed. In the various groups, the spinal cord ischemia model was made by the impediment of the aorta only caudal to the renal vein. Neurological assessment was conducted with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, similar to the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural assessments were additionally performed.
After ischemia-reperfusion injury, increments were found in the tissue myeloperoxidase levels ( < 0.001), malondialdehyde levels ( < 0.001), xanthine oxidase action ( < 0.001) and caspase-3 movement ( < 0.001). Conversely, both serum and tissue catalase levels were diminished ( < 0.001 for both). After the administration of tetracosactide, declines were seen in the tissue myeloperoxidase levels ( < 0.001), malondialdehyde levels ( = 0.003), xanthine oxidase action ( < 0.001) and caspase-3 movement ( < 0.001). Conversely, both the serum and tissue catalase levels were expanded ( < 0.001). Besides, tetracosactide treatment indicated enhanced results related to the histopathological scores ( < 0.001), the ultra-structural score ( = 0.008) and the Tarlov scores ( < 0.001).
The findings showed for the first time that tetracosactide shows significant neuroprotective activity against ischemia-reperfusion injury of the spinal cord.
替可克肽是一种人工合成肽,其生物学作用与内源性促肾上腺皮质激素相同。既往研究表明,替可克肽具有抗炎、抗氧化和神经营养活性。在本研究中,我们假设替可克肽可能对脊髓缺血再灌注损伤具有保护作用。
将家兔随机分为四组,每组8只:第1组(对照组)、第2组(缺血组)、第3组(甲基强的松龙组)和第4组(替可克肽组)。对照组仅行剖腹术。在其他各组中,通过仅在肾静脉尾侧阻断主动脉建立脊髓缺血模型。采用塔尔洛夫评分系统进行神经功能评估。分析髓过氧化物酶、丙二醛和过氧化氢酶水平,以及黄嘌呤氧化酶和半胱天冬酶-3的活性。另外进行组织病理学和超微结构评估。
缺血再灌注损伤后,组织髓过氧化物酶水平(<0.001)、丙二醛水平(<0.001)、黄嘌呤氧化酶活性(<0.001)和半胱天冬酶-3活性(<0.001)均升高。相反,血清和组织过氧化氢酶水平均降低(两者均<0.001)。给予替可克肽后,组织髓过氧化物酶水平(<0.001)、丙二醛水平(=0.003)、黄嘌呤氧化酶活性(<0.001)和半胱天冬酶-3活性(<0.001)均下降。相反,血清和组织过氧化氢酶水平均升高(<0.001)。此外,替可克肽治疗在组织病理学评分(<0.001)、超微结构评分(=0.008)和塔尔洛夫评分(<0.001)方面显示出更好的结果。
研究结果首次表明,替可克肽对脊髓缺血再灌注损伤具有显著的神经保护活性。