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The protective effects of omega-3 fatty acids against MK-801-induced neurotoxicity in prefrontal cortex of rat.

机译:ω-3脂肪酸对MK-801诱导的大鼠前额叶皮层神经毒性的保护作用。

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The aims of this study are to investigate the contribution effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Because oxidative damage has been suggested in the neuropathophysiology of schizophrenia, the possible protecting agents against lipid peroxidation are potential target for the studies in this field. For this purpose, Wistar Albino rats were divided into three groups: the first group was used as control, MK-801 was given to the rats in the second group and MK-801+omega-3 essential fatty acids (EFA) was given to the third group. MK-801 was given intraperitoneally at the dose of 0.5mg/(kgday) once a day for 5 days in experimental psychosis group. In the second group, 0.8g/(kgday), omega-3 FA (eicosapentaenoic acid, 18%, docosahexaenoic acid, 12%) was given to the rats while exposed MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal brain area was removed for histological and biochemical analyses. As a result, malondialdehyde (MDA), as an indicator of lipid peroxidation, protein carbonyl (PC), as an indicator of protein oxidation, nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities as antioxidant enzymes, and xanthine oxidase (XO) and adenosine deaminase (AD) activities as an indicator of DNA oxidation was found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (P<0.0001) compared to control group. In omega-3 FA treated rats, prefrontal tissue MDA, PC and NO levels as well as SOD, GSH-Px, XO, and AD enzyme activities were significantly decreased when compared to MK-801 groups (P<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. omega-3 FA supplementation decreased the apoptotic cell count in PFC. The results of this study revealed that oxidative stress and apoptotic changes in PFC may play an important role in the pathogenesis of MK-801-induced neuronal toxicity. This experimental study also provides some evidences for the protective effects of omega-3 FA on MK-801-induced changes in PFC of rats.
机译:这项研究的目的是调查氧化应激在MK-801诱发的实验性精神病模型中的作用,并表明预防氧化应激可以改善预后。因为在精神分裂症的神经病理生理学中已经提出了氧化损伤,所以针对脂质过氧化的可能的保护剂是该领域研究的潜在目标。为此,将Wistar Albino大鼠分为三组:第一组为对照组,第二组为MK-801,第二组为MK-801 + omega-3必需脂肪酸。第三组。在实验性精神病组中,以0.5mg /(kg·day)的剂量腹膜内给予MK-801,持续5天。在第二组中,在暴露于MK-801的同时,给大鼠服用0.8g /(kg·day)的omega-3 FA(二十碳五烯酸,18%,二十二碳六烯酸,12%)。对照组同时腹腔注射生理盐水。 7天后,通过断头处死大鼠。去除前额脑区域用于组织学和生化分析。结果,丙二醛(MDA)作为脂质过氧化的指标,蛋白质羰基(PC)作为蛋白质氧化的指标,一氧化氮(NO)水平和超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)活性与抗氧化剂相比,MK-801组的前额叶皮层(PFC)中的黄嘌呤氧化酶(XO)和腺苷脱氨酶(AD)活性作为DNA氧化的指标显着增加(P <0.0001)。与MK-801组相比,在经omega-3 FA治疗的大鼠中,前额组织MDA,PC和NO水平以及SOD,GSH-Px,XO和AD酶活性显着降低(P <0.0001),而过氧化氢酶(CAT )酶活性未改变。此外,根据MK-801组的显微镜检查,观察到大量的凋亡细胞。补充omega-3 FA可以减少PFC中的凋亡细胞数量。这项研究的结果表明,PFC中的氧化应激和凋亡变化可能在MK-801诱导的神经元毒性的发病机理中起重要作用。这项实验研究也为omega-3 FA对MK-801诱导的大鼠PFC改变的保护作用提供了一些证据。

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