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血管活性肠肽(VIP)对大鼠纹状体 6-羟多巴胺毒性的抗氧化和抗细胞凋亡作用。

Antioxidant and anti-apoptotic activity of vasoactive intestinal peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum.

机构信息

Department of Physiology, Faculty of Medicine, Eskişehir Osmangazi University, 26480, Eskişehir, Turkey.

出版信息

J Mol Neurosci. 2012 Jan;46(1):51-7. doi: 10.1007/s12031-011-9618-z. Epub 2011 Aug 18.

Abstract

6-Hydroxydopamine (6-OHDA) is an oxidative stress neurotoxin, which is oxidized in neurons, causes respiratory inhibition, and induces free radical formation and oxidative stress. Therefore, a 6-OHDA-induced Parkinson's disease (PD) experimental model can be used to test a candidate molecule for use as an antioxidant that could be a promising therapeutic for treating Parkinson's disease. Recent studies have shown that vasoactive intestinal peptide (VIP) might be a good candidate agent for the treatment of PD. In this study, the anti-apoptotic and antioxidant actions of VIP were investigated using the 6-OHDA-lesioned rat model for PD. Twenty-four young adult Sprague-Dawley rats were used. The rats were separated into the following groups: group I (n = 8), sham operated; group II (n = 8), 6-OHDA lesioned; group III (n = 8), 6-OHDA lesioned + i.p. VIP-injected (25 ng/kg) every 2 days for 15 days. The first i.p. injection of VIP was made 1 h after the intrastriatal 6-OHDA microinjection. Antioxidant enzymatic activity [super oxide dismutase (SOD) and catalase (CAT)], lipid peroxidation, nitric oxide and DNA fragmentation were measured from homogenates isolated from the corpus striatum. SOD, CAT, malondialdehyde, and DNA fragmentation were measured using a spectrophotometer, and nitric oxide (NO) levels were measured by capillary electrophoresis. 6-OHDA significantly induced oxidative stress, lipid peroxidation, and DNA fragmentation in the corpus striatum of rats. VIP significantly protected neuronal tissue from oxidative stress and apoptosis by reducing lipid peroxidation and DNA fragmentation. 6-OHDA toxicity did not cause significant changes in NO production in the corpus striatum. However, VIP treatment significantly reduced NO levels in brain tissue.

摘要

6-羟多巴胺(6-OHDA)是一种氧化应激神经毒素,在神经元中被氧化,导致呼吸抑制,并诱导自由基形成和氧化应激。因此,6-OHDA 诱导的帕金森病(PD)实验模型可用于测试候选抗氧化分子,该分子可能是治疗帕金森病的有前途的治疗方法。最近的研究表明,血管活性肠肽(VIP)可能是治疗 PD 的良好候选药物。在这项研究中,使用 6-OHDA 损伤的 PD 大鼠模型研究了 VIP 的抗凋亡和抗氧化作用。使用 24 只年轻成年 Sprague-Dawley 大鼠。大鼠被分为以下几组:第 I 组(n = 8),假手术;第 II 组(n = 8),6-OHDA 损伤;第 III 组(n = 8),6-OHDA 损伤+腹腔注射 VIP(25ng/kg),每 2 天一次,共 15 天。第一次腹腔注射 VIP 是在纹状体 6-OHDA 微注射后 1 小时进行的。从纹状体匀浆中测量抗氧化酶活性[超氧化物歧化酶(SOD)和过氧化氢酶(CAT)]、脂质过氧化、一氧化氮和 DNA 片段化。使用分光光度计测量 SOD、CAT、丙二醛和 DNA 片段化,使用毛细管电泳测量一氧化氮(NO)水平。6-OHDA 显著诱导大鼠纹状体的氧化应激、脂质过氧化和 DNA 片段化。VIP 通过减少脂质过氧化和 DNA 片段化,显著保护神经元组织免受氧化应激和细胞凋亡。6-OHDA 毒性不会导致纹状体中 NO 产生的显著变化。然而,VIP 处理显著降低了脑组织中的 NO 水平。

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