琐琐葡萄多糖对阿尔茨海默病大鼠学习记忆能力及氧化应激的影响

Effect of polysaccharides extracted from vitis vinifera L. on learning and memory abilities and oxidative stress in rats with Alzheimer's disease

目的探讨琐琐葡萄多糖(VTP)对阿尔茨海默病(AD)大鼠学习记忆能力和氧化应激的影响以及可能的保护作用机制。方法将60只雄性SD大鼠随机分为6组(=10):正常对照组、模型对照组、阳性对照组(多耐哌齐0.5 mg/kg)、VTP低(50 mg/kg)、中(150 mg/kg)、高(300 mg/kg)剂量组。除正常对照组外,余各组大鼠正常喂养1周后,通过在海马区注射β淀粉样蛋白(Aβ)_(25-35)的方法建立AD模型,随后模型对照组大鼠给予蒸馏水灌胃,余各组给予相应药物灌胃15 d。通过Y迷宫实验进行认知功能评价;检测血清和海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性和丙二醛含量。结果与正常对照组比较,模型对照组Y迷宫测试错误次数明显增多,总反应时间明显延长,达到标准所需次数明显增多[(6.2±1.5)次比(1.8±0.8)次、(158±19)s比(86±16)s、(92±8)次比(57±8)次],差异均有统计学意义(均P<0.05);与模型对照组比较,阳性对照组、VTP多糖中、高剂量组测试错误次数明显减少[(2.2±0.8)、(2.7±1.2)、(1.8±0.8)次],总反应时间明显缩短[(87±15)、(89±14)、(83±16)s],达到标准所需次数明显减少[(60±9)、(75±8)、(63±10)次],差异均有统计学意义(均P<0.05)。与正常对照组比较,模型对照组血清和海马组织中SOD、GSH-Px、CAT活性明显降低,丙二醛含量明显升高,差异均有统计学意义(均P<0.05)。与模型对照组比较,阳性对照组、VTP中、高剂量组血清和海马组织中SOD、GSH-Px、CAT活性明显升高,丙二醛含量明显降低,差异均有统计学意义(均P<0.05);VTP低剂量组海马组织中SOD、GSH-Px、CAT活性明显升高,丙二醛含量明显降低,差异均有统计学意义(均P<0.05)。结论 VTP能够改善AD大鼠的学习记忆能力,可能通过影响氧化应激反应来拮抗Aβ的神经毒性而起作用。

Objective To investigate the effect of polysaccharides extracted from vitis vinifera L. （VTP） on learning and memory abilities and oxidative stress in Alzheimer＇s disease（AD） rats. Methods Sixty male SD rats were randomly divided into 6 groups （n =10 ） ： normal control group, model control group, positive control group（polyphenidazole 0. 5 mg/kg） , low dose VTP（50 mg/kg） group, middle dose VTP（ 150 mg/kg） group and high dose VTP（300 mg/kg） group. Rats in model control group, positive control group, low, middle and high dose VTP groups were made AD models by hippocampal injection of amyloid-β（Aβ）. The model control group had distilled water gavage and other groups had drug gavage for 15 d. Cognitive function was evaluated by the Y-maze test. Indicators of oxidative stress in serum and hippocampus were detected, including superoxide dismutase （SOD）, glutathione peroxidase（GSH-Px）, catalase（CAT） and malondialdehyde（MDA）. Results Number of Y-maze test errors in model control group was significantly more, total reaction time was significantly longer and number of tests before meeting the standard was significantly more than those in normal control group [ （ 6.2 ± 1.5）timesvs （1.8±0.8）times, （158±19）s vs （86±16）s, （92±8）times vs （57 ±8）times]（P〈0.05）. Number of test errors in positive control group, middle and high dose VTP groups [ （ 2.2± 0. 8 ） , （ 2. 7 ±1.2 ） , （1.8 ± 0. 8 ）times] was significantly less, total reaction time[ （87 ± 15 ）, （89 ± 14 ）, （83 ± 16 ）s ] was significantly shorter and number of tests before meeting the standard [ （60 ± 9 ） , （ 75 ± 8 ）, （ 63 ± 10 ） times ] was significantly less than those in model control group （ P 〈 0. 05 ）. Levels of SOD, GSH-Px and CAT in serum and hippocmnpus in model control group were significantly lower and MDA was significantly higher than those in normal control group （ P 〈 0. 05 ）. Levels of SOD, GSH-Px and CAT in serum and hippocampus in positive control group, middle and high dose VTP groups were significantly higher and MDA was significantly lower than those in model control group （ P 〈 0. 05 ）. Levels of SOD, GSH-Px and CAT in hippocampus in low dose VTP group were significantly higher and MDA was significantly lower than those in model control group （P 〈 0. 05 ）. Conclusion VTP can antagonize the neurotoxicity of Aβ by affecting oxidative stress response to improve learning and memory abilities of AD rats.