琐琐葡萄黄酮对APP/PS-1双转基因阿尔茨海默病小鼠神经炎症的保护作用

Protective effect of flavones from vitis vinifera L on neuroinflammation in APP/PS-1 double transgenic Alzheimer's disease mice

目的研究琐琐葡萄黄酮(VTF)对APP/PS-1双转基因阿尔茨海默病(AD)小鼠神经炎症保护作用的机制。方法选取6月龄APP/PS-1双转基因雄性小鼠75只,随机分为模型组(0.5%CMC-Na)、阳性组(多奈哌齐0.7 mg/kg体重)、VTF低剂量组(VTF 70 mg/kg体重)、VTF中剂量组(VTF 210 mg/kg体重)、VTF高剂量组(VTF 420 mg/kg体重),每组15只;另选取6月龄同背景SPF级C57BL/6小鼠15只为对照组(0.5%CMC-Na)。灌胃8周后,免疫组织化学检测IBA1蛋白表达;Western blotting检测APP、IBA1蛋白表达;酶联免疫吸附试验(ELISA)检测脑组织的白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的含量。结果对照组、阳性组及VTF各剂量组IBA1蛋白阳性表达率较模型组低(P<0.05);对照组、阳性组及VTF各剂量组APP、IBA1蛋白相对表达量较模型组低(P<0.05);对照组、阳性组及VTF各剂量组IL-1β、IL-6、TNF-α含量较模型组减少(P<0.05)。结论VTF可以减少APP/PS-1双转基因AD小鼠神经炎症的发生,并通过下调APP、IBA1蛋白的表达发挥神经保护作用。

Objective To investigate the neuroprotective effect of flavones from vitis vinifera L(VTF)on APP/PS-1 double transgenic mice model of Alzheimer's disease(AD).Methods Seventy-five 6-month-old APP/PS-1 double transgenic male mice were randomly divided into model group(0.5%CMC-NA)and donepezil group(0.7 mg/kg)and low,medium,and high dose VTF group(70 mg/kg,210 mg/kg,and 420 mg/kg),15 mice in each group,and 156-month-old C57BL/6 mice with the same background SPF level were used as the wild control group(0.5%CMC-NA).All drug solvents were 0.5%CMC-Na solution.After 8 weeks of gavage,IBA1 protein expression was detected via immunohistochemistry and Western blotting.The protein expression levels of APP and Iba1 were detected by Western blotting.The contents of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF-α)in brain tissue were detected by ELISA.Results Compared with the model group,immunohistochemical results showed that the number of IBA1 protein positive cells was significantly reduced in the wild control,donepezil,low,medium,and high dose VTF group;WB results showed that the relative expressions of APP and IBA1 protein in the wild control,donepezil,low,medium,and high dose VTF group were decreased;ELISA results showed that the levels of IL-1β,IL-6,TNFαwere significantly decreased in the wild control,donepezil,low,medium,and high dose VTF group.Conclusion VTF can reduce the occurrence of neuroinflammation in APP/PS-1 mice,reduce the damage of hippocampal neurons,and play a protective role by down-regulating the expression levels of APP and Iba1 proteins.