| 再娜甫古丽·买买提,马心念,古力夏提·艾力,张 鹏,袁 芳.齐墩果酸对APP/PS-1双转基因AD小鼠的神经保护作用研究[J].现代生物医学进展英文版,2023,(24):4614-4619. |
| 齐墩果酸对APP/PS-1双转基因AD小鼠的神经保护作用研究 |
| The Effect of Oleanolic Acid on APP/PS-1 Double Transgenic AD Mice |
| Received:May 28, 2023 Revised:June 23, 2023 |
| DOI：10.13241/j.cnki.pmb.2023.24.003 |
| 中文关键词: 阿尔茨海默病 APP/PS-1双转基因AD小鼠 齐墩果酸 β淀粉样蛋白 |
| 英文关键词: Alzheimer's disease APP/PS-1 double transgenic AD mice Oleanolic acid Beta amyloid |
| 基金项目:国家自然科学基金项目（81960764） |
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| 中文摘要: |
| 摘要 目的：研究齐墩果酸（Oleanolic Acid，OA）对APP/PS-1双转基因阿尔茨海默病（Alzheimer's disease，AD）小鼠模型神经保护作用及机制。方法：选取6月龄APP/PS-1雄性小鼠21只，随机分为模型组（0.5% CMC-Na）、阳性组（多奈哌齐组，0.7 mg?kg-1）、齐墩果酸组（10 mg?kg-1）每组7只，6月龄同背景SPF级C57BL/6小鼠7只为对照组。灌胃8周之后通过Morris水迷宫实验观察小鼠学习记忆能力的改变，HE染色观察神经元细胞形态，ELISA检测血清中Aβ1-42含量；免疫组化检测Aβ1-42、APP、Iba1蛋白表达情况；Western blot检测APP、Iba1蛋白表达水平。结果：（1）对照组，模型组，阳性组及齐墩果酸组进入有效区域次数分别为7.00±2.09，1.00±0.89，3.67±1.97，4.33±2.50，与模型组相比，对照组，阳性组，齐墩果酸组均有统计学意义（P<0.05）；（2）血清Aβ1-42含量按上述顺序依次为4.98±0.25，2.50±0.66，4.63±0.73，4.36±0.97，与模型组相比，对照组，阳性组，齐墩果酸组均有统计学意义（P<0.05）；（3）免疫组化结果显示与模型组相比，对照组，阳性组，齐墩果酸组Aβ1-42、APP、Iba1蛋白阳性细胞数减少；（4）WB结果：对照组，模型组，阳性组，齐墩果酸组APP蛋白相对表达量分别为0.52±0.17，1.38±0.35，0.89±0.25，0.93±0.27；这四组的IBA1蛋白相对表达量分别为0.98±0.34，1.79±0.74，1.06±0.61，0.88±0.49，与模型组相比，野生对照组，阳性组，齐墩果酸组APP、IBA1蛋白相对含量有统计学意义（P<0.05）。结论：齐墩果酸组可以改善APP/PS-1模型小鼠记忆力及认知功能，降低海马神经元的损伤，并通过下调Aβ1-42、APP、Iba1蛋白的表达水平来发挥保护神经作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the brain protection mechanism of oleanolic acid on APP/PS-1 double transgenic mice with Alzheimer's disease (AD). Methods: 21 6-month-old AD mice were casually divided into model group (0.5% CMC-Na), positive administration group (donepezil group, 0.7 mg?kg-1) and oleanolic acid group (10 mg?kg-1), while C57BL/6 mice were chosen as control group. 8 weeks later, we use water maze to observe the spatial cognitive ability of mice. He staining was used to observe the morphology of neurons, and ELISA was used to detect the content of Aβ1-42 in serum. The protein expression levels of Aβ1-42, APP and Iba1 were detected by immunohistochemistry. Western blot used to detect APP and Iba1 protein expression levels. Results: (1) The Times of entering effective area in control group, model group, positive group and oleanolic acid group were 7.00±2.09, 1.00±0.89, 3.67±1.97, 4.33±2.50. Compared with model group, control group, positive group and oleanolic acid group was significantly increased (P<0.05). (2) The contents of Aβ1-42 in serum were 4.98±0.25, 2.50±0.66, 4.63±0.73 and 4.36±0.97, compared with model group, wild control group, positive group and oleanolic acid group was significantly reduced(P<0.05); (3) Compared with model group, the number of Aβ1-42, APP and Iba1 protein positive cells in control group, positive group and oleanolic acid group decreased; (4) WB results The relative expression of APP protein in wild control group, model group, positive group and oleanolic acid group were 0.52±0.17, 1.38±0.35, 0.89±0.25 and 0.93±0.27. The relative expression levels of IBA1 protein in the four groups were 0.98±0.34, 1.79±0.74, 1.06±0.61 and 0.88±0.49. Compared with the model group, the relative content of APP and IBA1 protein in the wild control group, positive group and oleanolic acid group was significantly decreased(P<0.05). Conclusion: Oleanolic acid group can protect the memory and cognitive function of APP/PS-1 model mice, reduce the damage of hippocampal neurons, and play a neuroprotective role by down-regulating the expression levels of Aβ1-42, APP and Iba1 proteins. |
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