帕金森病(Parkinson′s disease, PD)的重要发病机制之一是氧化应激,而壳寡糖具有较好的抗氧化活性且在PD等神经性疾病中具有良好的保护效果。将小鼠分为空白组、模型组、低剂量组(35 mg/kg)、中剂量组(70 mg/kg)和高剂量组(140 mg/kg),利用1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)对小鼠腹腔注射诱导PD模型,并通过行为学、病理指标和氧化应激相关指标对各组小鼠进行评估,探究了壳三糖对于PD小鼠保护效果的量效关系及保护机制。结果显示,低中高3个剂量组壳三糖均能缓解PD小鼠的行为学障碍和纹状体中酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量的减少,且中剂量组效果最佳。壳三糖干预显著降低了PD小鼠纹状体中丙二醛(malondialdehyde, MDA)含量,提高了还原型谷胱甘肽(glutathione, GSH)含量、总抗氧化能力(total antioxidant capacity, T-AOC)以及过氧化氢酶(catalase, CAT)、超氧化物歧化酶(superoxide dismutase, SOD)的表达,上调了核因子E2相关因子(NF-E2-related factor 2, Nrf2)/血红素氧化酶(heme oxygenase, HO-1)信号通路。结果表明,中剂量壳三糖对MPTP诱导的PD有更明显的缓解作用,其作用机制可能是通过提高抗氧化酶表达和上调Nrf2/HO-1信号通路,降低PD小鼠氧化应激从而缓解PD。
Oxidative stress is one of the important pathogenesis of Parkinson's disease (PD), and chitosan oligosaccharides have good antioxidant activity and protective effects in neuropathic diseases such as PD.The mice were divided into a control group, model group, low dose group (35 mg/kg), medium dose group (70 mg/kg), and high dose group (140 mg/kg).The mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD mice models.To explore the dose-effect relationship and protective mechanism of chitotriose in PD mice, the mice in each group were evaluated by behavioral and pathological indexes and the related indexes of oxidative stress.Results showed that low, middle, and high doses of chitotriose could alleviate the behavioral disorder and the decrease of tyrosine hydroxylase (TH) expression in the striatum of PD mice, and the middle dose group had the best effect.The chitotriose intervention significantly reduced the content of malondialdehyde (MDA) in the striatum of PD mice, significantly increased the levels of glutathione (GSH), total antioxidant capacity (T-AOC), catalase (CAT), and superoxide dismutase (SOD), and up-regulated the nuclear factor E2 related factor (Nrf2)/heme oxygenase (HO-1) signal pathway.Results indicated that the middle dose of chitotriose had a more obvious alleviating effect on MPTP-induced PD mice.The mechanism of its action may be to reduce oxidative stress and alleviate PD by increasing the expression of antioxidant enzymes and up-regulating the Nrf2/HO-1 signaling pathway.
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