琐琐葡萄黄酮对APP/PS-1小鼠海马神经细胞凋亡的影响  

Effect of Flavones from Vitis Vinifera L on Apoptosis of Hippocampal Neurons in APP/PS-1 Mice

作　　者：古力夏提·艾力 肖辉[1] 再娜甫古丽·买买提 张鹏 袁芳[2] GULIXIATI·Aili;XIAO Hui;ZAINAFUGULI·Maimaiti(School of Public Health,Xinjiang Medical University,Xinjiang 830011,China)

机构地区：[1]新疆医科大学公共卫生学院,乌鲁木齐830011 [2]新疆医科大学基础医学院,乌鲁木齐830011

出　　处：《医学研究杂志》2023年第4期41-44,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81960764)。

摘　　要：目的 探讨琐琐葡萄总黄酮(flavones from vitis vinifera L.,VTF)对APP/PS-1双转基因阿尔茨海默病(Alzheimer′s disease, AD)小鼠海马神经细胞凋亡的影响。方法 选用6月龄雄性APP/PS-1双转基因AD小鼠75只,随机分为模型组,阳性对照组(多奈哌齐组,0.7mg/kg),VTF低、中、高剂量组(70、210、420mg/kg),另取15只同龄雄性C57BL/6小鼠作为空白对照组,模型组和空白对照组给予等量0.5%CMC-Na灌胃。酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测小鼠血清中Aβ1~42含量;免疫组织化学(immunohistodiemistiy, IHC)观察小鼠海马CA1区caspase-3蛋白表达情况;原位末端标记(TdT-mediated dUTP-biotin nick end labeling assay, TUNEL)法检测小鼠海马神经细胞凋亡情况。结果 ELISA检测结果显示,与模型组比较,阳性对照组和VTF各剂量组小鼠血清中Aβ1~42含量显著升高(P<0.05)。IHC实验结果显示,模型组小鼠海马CA1区caspase-3蛋白表达与空白对照组比较,阳性细胞着色深(P<0.05),VTF各剂量组小鼠较模型组海马caspase-3蛋白阳性表达均有所减少(P<0.05)。TUNEL法检测结果显示,与模型组比较,阳性对照组及VTF各剂量组小鼠海马神经元细胞大多较正常,其凋亡率与模型组比较显著下降(P<0.05)。结论 VTF可以通过下调caspase-3蛋白的表达从而减少APP/PS-1双转基因AD小鼠海马神经元的凋亡,对APP/PS-1双转基因AD小鼠具有较好的防治作用。Objective To investigate the effect of flavones from vitis vinifera L.(VTF)on hippocampal neurons apoptosis in APP/PS-1double transgenic AD mice.Methods Seventy-five 6-month-old male APP/PS-1double transgenic AD mice were randomly divided into model group,positive control group(donepezil group,0.7mg/kg),VTF low-dose,medium-dose and high-dose groups(70,210 and 420mg/kg),and 15male C57BL/6mice of the same age were taken as blank control group.The model group and blank control group were given the same amount of 0.5%CMC-Na by gavage.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of Aβ1-42 in serum of mice;immunohistochemical(IHC)staining was used to observe the expression of caspase-3 protein in hppocampal CA1 region of mice;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)method was used to detect the apoptosis of hippocampal neurons in mice.Results The results of ELISA showed that compared with the model group,the content of Aβ1-42 in serum of mice in the positive control group and VTF dose groups was significantly increased(P<0.05).The results of IHC experiment showed that the expression of caspase-3 protein in hippocampal CA1 region in the model group was darker than that in the blank control group(P<0.05),and the positive expression of caspase-3 protein in hippocampal CA1 region of mice in the VTF dose groups was decreased compared with that in the model group(P<0.05).TUNEL assay showed that compared with the model group,most hippocampal neurons in the positive control group and VTF dose groups were normal,and the apoptosis rate was significantly decreased compared with the model group(P<0.05).Conclusion VTF can reduce the apoptosis of hippocampal neurons in APP/PS-1 transgenic mice by down-regulating the expression of caspase-3 protein,and has a good preventive and therapeutic effect on APP/PS-1double transgenic AD mice.

关 键 词：琐琐葡萄黄酮 阿尔茨海默病 APP/PS-1双转基因AD小鼠 凋亡 

分 类 号：R749.16[医药卫生—神经病学与精神病学]