PDF(Pubmed)
Abstract：
OBJECTIVE: To investigate the effect of vanillic acid (VA) on a Cuprizone (Cup) demyelinating rat model and the mechanisms behind such effect.
METHODS: Thirty adult male Sprague Dawley (SD) rats were randomly divided into three groups: control, Cuprizone, and VA groups. Cuprizone was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks. The nerve conduction velocity (NCV) was studied in an isolated sciatic nerve, and then the sciatic nerve was isolated for histopathological examination, electron microscope examination, immunohistochemical staining, and biochemical and PCR assay. The level of IL17 was detected using ELISA, while the antioxidant genes Nrf2, HO-1 expression at the level of mRNA, expression of the myelin basic protein (MBP), interferon-gamma factor (INF)-γ and tumor necrosis factor (TNF)-α, and apoptotic marker (caspase-3) were measured using immunohistochemistry in the sciatic nerve.
RESULTS: There was a significant reduction in NCV in Cup compared to normal rats (p < 0.001), which was markedly improved in the VA group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers with significant improvement in the VA group. The level of IL17 as well as the expression of INF-γ and caspase-3 were significantly increased with a significant reduction in the expression of MBP, Nrf2, and HO-1 in the sciatic nerve (p < 0.01), and VA treatment significantly improved the studied parameters (p < 0.01).
CONCLUSIONS: The current study demonstrated a neuroprotective effect for VA against the Cup-induced demyelinating rat model. This effect might be precipitated by the inhibition of inflammation, oxidative stress, and apoptosis.
METHODS: Thirty adult male Sprague Dawley (SD) rats were randomly divided into three groups: control, Cuprizone, and VA groups. Cuprizone was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks. The nerve conduction velocity (NCV) was studied in an isolated sciatic nerve, and then the sciatic nerve was isolated for histopathological examination, electron microscope examination, immunohistochemical staining, and biochemical and PCR assay. The level of IL17 was detected using ELISA, while the antioxidant genes Nrf2, HO-1 expression at the level of mRNA, expression of the myelin basic protein (MBP), interferon-gamma factor (INF)-γ and tumor necrosis factor (TNF)-α, and apoptotic marker (caspase-3) were measured using immunohistochemistry in the sciatic nerve.
RESULTS: There was a significant reduction in NCV in Cup compared to normal rats (p < 0.001), which was markedly improved in the VA group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers with significant improvement in the VA group. The level of IL17 as well as the expression of INF-γ and caspase-3 were significantly increased with a significant reduction in the expression of MBP, Nrf2, and HO-1 in the sciatic nerve (p < 0.01), and VA treatment significantly improved the studied parameters (p < 0.01).
CONCLUSIONS: The current study demonstrated a neuroprotective effect for VA against the Cup-induced demyelinating rat model. This effect might be precipitated by the inhibition of inflammation, oxidative stress, and apoptosis.
摘要：
目的：为了研究香草酸（VA）对Cuprizone（Cup）脱髓鞘大鼠模型的作用以及这种作用背后的机制。
方法:成年雄性SD大鼠30只,随机分为3组:对照组,Cuprizone,和VA组。Cuprizone以450mg/kg/天的剂量经胃灌胃给药5周。在孤立的坐骨神经中研究了神经传导速度（NCV），然后分离坐骨神经进行组织病理学检查，电子显微镜检查，免疫组织化学染色，生化和PCR检测。使用ELISA检测IL17的水平，而抗氧化基因Nrf2、HO-1在mRNA水平表达,髓鞘碱性蛋白（MBP）的表达，干扰素-γ因子（INF）-γ和肿瘤坏死因子（TNF）-α，和凋亡标志物（caspase-3）使用免疫组织化学在坐骨神经中进行测量。
结果：与正常大鼠相比，Cup的NCV显着降低（p<0.001），VA组明显改善（p<0.001）。EM和组织病理学检查显示，VA组的坐骨神经纤维明显脱髓鞘和恶化，并有显着改善。IL17的水平以及INF-γ和caspase-3的表达显着增加，MBP的表达显着降低，坐骨神经中的Nrf2和HO-1（p<0.01），和VA处理显着改善了研究参数（p<0.01）。
结论：本研究证明了VA对Cup诱导的脱髓鞘大鼠模型的神经保护作用。这种效应可能是通过抑制炎症来沉淀的，氧化应激，和凋亡。
方法:成年雄性SD大鼠30只,随机分为3组:对照组,Cuprizone,和VA组。Cuprizone以450mg/kg/天的剂量经胃灌胃给药5周。在孤立的坐骨神经中研究了神经传导速度（NCV），然后分离坐骨神经进行组织病理学检查，电子显微镜检查，免疫组织化学染色，生化和PCR检测。使用ELISA检测IL17的水平，而抗氧化基因Nrf2、HO-1在mRNA水平表达,髓鞘碱性蛋白（MBP）的表达，干扰素-γ因子（INF）-γ和肿瘤坏死因子（TNF）-α，和凋亡标志物（caspase-3）使用免疫组织化学在坐骨神经中进行测量。
结果：与正常大鼠相比，Cup的NCV显着降低（p<0.001），VA组明显改善（p<0.001）。EM和组织病理学检查显示，VA组的坐骨神经纤维明显脱髓鞘和恶化，并有显着改善。IL17的水平以及INF-γ和caspase-3的表达显着增加，MBP的表达显着降低，坐骨神经中的Nrf2和HO-1（p<0.01），和VA处理显着改善了研究参数（p<0.01）。
结论：本研究证明了VA对Cup诱导的脱髓鞘大鼠模型的神经保护作用。这种效应可能是通过抑制炎症来沉淀的，氧化应激，和凋亡。
