Toklu Hale Z, Hakan Tayfun, Celik Hasan, Biber Necat, Erzik Can, Ogunc Ayliz V, Akakin Dilek, Cikler Esra, Cetinel Sule, Ersahin Mehmet, Sener Goksel
Marmara University School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
J Spinal Cord Med. 2010;33(4):401-9. doi: 10.1080/10790268.2010.11689719.
Oxidative stress is a mediator of secondary injury to the spinal cord following trauma.
To investigate the putative neuroprotective effect of alpha-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI).
Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique.
SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged.
The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.
氧化应激是创伤后脊髓继发性损伤的介导因素。
在大鼠脊髓损伤模型中研究强效抗氧化剂α-硫辛酸(LA)假定的神经保护作用。
将Wistar白化大鼠分为对照组、溶剂处理的脊髓损伤组和LA处理的脊髓损伤组。采用标准的重物坠落法在T10诱导中度严重损伤(100 g/cm力)以造成脊髓损伤。损伤动物在伤后30分钟通过腹腔注射给予50 mg/kg LA或生理盐水。在伤后7天进行神经学检查,然后将大鼠断头。采集脊髓样本进行组织学检查或测定丙二醛(MDA)和谷胱甘肽(GSH)水平、髓过氧化物酶(MPO)活性及DNA片段化情况。采用化学发光(CL)技术监测脊髓组织样本中活性氧的形成。
脊髓损伤导致脊髓GSH含量显著降低,同时鲁米诺CL和MDA水平、MPO活性及DNA损伤显著增加。此外,LA处理逆转了所有这些生化参数以及脊髓损伤诱导的组织病理学改变。相反,脊髓损伤所致神经功能损害保持不变。
本研究提示,LA可减轻脊髓损伤诱导的氧化应激,并通过抑制脂质过氧化、谷胱甘肽耗竭及DNA片段化发挥神经保护作用。