银杏叶提取物对阿尔茨海默病大鼠海马bFGF/Notch1通路的影响

赵萍; 李新; 崔静; 夏晓爽; 田文杰

doi:10.16766/j.cnki.issn.1674-4152.002041

银杏叶提取物对阿尔茨海默病大鼠海马bFGF/Notch1通路的影响

doi: 10.16766/j.cnki.issn.1674-4152.002041

赵萍^1, ,,
李新¹,
崔静²,
夏晓爽¹,
田文杰¹

1.
天津医科大学第二医院神经内科，天津 300211
2.
天津医科大学第二医院中医科，天津 300211

基金项目:

天津市卫生健康委中西医结合科研课题 2017162

详细信息

通讯作者:
赵萍，E-mail：supertongtong@163.com

中图分类号: R741.05 R-33
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- 被引次数: 0
出版历程
- 收稿日期: 2020-04-20
- 网络出版日期: 2022-02-16

Effect of Ginkgo biloba extract on bFGF/Notch1 pathway in hippocampus of rats models with Alzheimer's disease

1.
Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China

摘要

摘要: 目的本研究旨在探讨银杏叶提取物修复与Aβ25-35相关的阿尔茨海默病(Alzheimer's disease，AD)大鼠神经元的作用机制。方法按照随机数字表法将筛选合格的60只大鼠分为模型组、正常对照组、假手术组(各10只)和银杏叶实验组(高、中、低剂量3组各10只)，通过鞘内注射Aβ25-35进行模型构造。通过Morris水迷宫实验测试各组大鼠记忆及学习能力，采用免疫印迹法检测各组大鼠的海马组织中碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)、多毛分裂增强子(hairy enhancer of split1, Hes1)、缺口同系物1(Notch homolog 1，Notch1)和转录因子重组信号结合蛋白JK(recombination signal binding protein-JK，RBP-JK)蛋白的表达量。结果 AD模型组大鼠寻找平台时间[(60.190±3.821)s]显著长于对照组(P＜0.05)，找到原来位置次数[(4.310±2.057)次]明显减少，差异有统计学意义(P＜0.05)；与模型组相比，银杏叶高、中、低剂量组寻找平台时间显著减少(均P＜0.05)，跨台次数明显比模型组多(均P＜0.05)。与对照组比较，模型组bFGF(0.542±0.036)、Notch1(0.185±0.032)和Hes1(0.153±0.022)蛋白表达量均显著减少，而RBP-JK蛋白表达量(0.800±0.047)显著增多(均P＜0.05)；而银杏叶高、中、低剂量组的海马组织bFGF、Notch1和Hes1蛋白表达量较模型组高(均P＜0.05)，RBP-JK蛋白表达量较模型组减少(均P＜0.05)。结论银杏叶提取物可能通过激活Notch通路，促进Notch1、bFGF和Hes1的表达，抑制RBP-JK的表达，从而改善AD大鼠的学习能力和记忆能力。
- 阿尔茨海默病 /
- 大鼠模型 /
- 银杏叶提取物
Abstract: Objective To explore the mechanism of Ginkgo biloba extract (GBE) in repairing AD rats' neurons related to Aβ25-35. Methods According to the random method, 60 rats meeting the requirements were divided into model group, normal control group, sham operation group, Ginkgo biloba experimental group (high, medium, low), 10 rats in each group. Model was built by intrathecal injection of Aβ25-35. All rats were studied by testing the memory and learning abilities were tested by Morris water maze. The expression levels of RBP-JK, Hes1, bFGF and Notch1 protein in hippocampus were detected by immunoblotting method. Results The time of finding platform in the AD model group [(60.190±3.821) s] was significantly longer than that in the normal control group (P < 0.01), and the frequency of finding the original platform position (4.310±2.057) was significantly reduced (P < 0.01). Compared with the model group, the time of finding the platform for the first time in the Ginkgo biloba high, middle and low dose groups were significantly reduced (P < 0.05), and the number of crossing platform was significantly more than that in the model group (all P < 0.01). The expression of bFGF (0.542±0.036), Notch1 (0.185±0.032) and Hes1 (0.153±0.022) in the model group were significantly decreased, while RBP-JK protein expression (0.800±0.047) was significantly increased (all P < 0.01). The protein expression of bFGF, Notch1 and Hes1 in the hippocampus of the Ginkgo biloba extract high, middle and low group were higher than that in the model group (all P < 0.05), while the protein expression of RBP-JK was decreased (all P < 0.05). Conclusion Ginkgo biloba extract may promote the expression of Notch1, bFGF and Hes1 and inhibit the expression of RBP-JK by activating the Notch pathway, thereby improving the learning ability and memory ability of AD rats.
- Alzheimer's disease /
- Rat model /
- Ginkgo biloba extract

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表 1 各组大鼠找到平台的时间及找到原来位置的次数比较(x ±s)

组别	只数	找到平台时间(s)	找到原来位置次数(次)
正常对照组	10	20.981±3.736	13.467±2.031
假手术组	10	21.894±3.785	12.667±2.289
模型组	10	60.190±3.821^ab	4.310±2.057^ab
银杏叶高剂量组	10	25.990±2.001^abc	11.000±1.964^abc
银杏叶中剂量组	10	30.222±2.404^abcd	8.667±1.839^abcd
银杏叶低剂量组	10	42.752±2.834^abcd	7.687±2.217^abcd
F值		206.815	40.066
P值		＜0.001	＜0.001
注：与正常对照组比较，^aP＜0.05；与假手术组比较，^bP＜0.05；与模型组比较，^cP＜0.05;与银杏叶高剂量组比较，^dP＜0.05。

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表 2 各组大鼠海马组织bFGF、Notch1、Hes1、RBP-JK蛋白相对表达量比较(x ±s)

组别	只数	bFGF	Notch1	Hes1	RBP-JK
正常对照组	10	1.362±0.031	0.512±0.061	0.522±0.065	0.229±0.025
假手术组	10	1.342±0.045	0.501±0.044	0.500±0.044	0.236±0.041
模型组	10	0.542±0.036^ab	0.185±0.032^ab	0.153±0.022^ab	0.800±0.047^ab
银杏叶高剂量组	10	0.933±0.071^c	0.468±0.047^c	0.428±0.034^c	0.287±0.045^c
银杏叶中剂量组	10	0.859±0.062^c	0.424±0.031^c	0.387±0.026^c	0.334±0.027^abc
银杏叶低剂量组	10	0.811±0.350^abcd	0.368±0.036^cd	0.282±0.043^abcd	0.416±0.045^abcd
F值		162.394	47.597	69.912	183.114
P值		＜0.001	＜0.001	＜0.001	＜0.001
注：与正常对照组蛋白含量比较，^aP＜0.05；与假手术组比较，^bP＜0.05；与模型组比较，^cP＜0.05；与银杏叶高剂量组比较，^dP＜0.05。

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