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白藜芦醇和大豆异黄酮对衰老模型大鼠学习记忆能力及葡萄糖转运蛋白表达的影响

[Effects of resveratrol and soy isoflavones on learning and memory ability and expression of glucose transporter in aging model rats].

作者信息

Zhang Luping, Yang Qian, Zhang Yusen, Li Xuemin, Dong Ruirui, Song Chenmeng, Cheng Le, Zhao Haifeng

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

Shanxi Center for Disease Control and Prevention, Taiyuan 030001, China.

出版信息

Wei Sheng Yan Jiu. 2020 Mar;49(2):249-253. doi: 10.19813/j.cnki.weishengyanjiu.2020.02.014.

Abstract

OBJECTIVE

To investigate the effects of resveratrol combined with soy isoflavones on avoidance memory, number of neuron-specific nuclear protein(NeuN) positive cells and expressions of glucose transporter(GLUT)1 and GLUT3 in hippocampus of aging model rats.

METHODS

A total of 60 female SD rats were randomly divided into 6 groups including sham control group, aging model group, 80 mg/kg resveratrol group, 160 mg/kg soy isoflavones group, 80 mg/kg resveratrol +160 mg/kg soy isoflavones group, 0. 8 mg/kg estradiol valerate group. The aging model rats was induced by ovariectomy combined with intraperitoneal injection of 100 mg/kg D-galactose. Intragastric administration was performed once a day for 12 weeks. The avoidance task was measured by the shuttle box test. The NeuN expression were measured by the immunofluorescence. The genes and proteins expression of GLUT1 and GLUT3 in rat hippocampus were detected by real-time PCR and Western blot, respectively.

RESULTS

Compared with the sham control group, the avoidance latency in the aging model group was prolonged, and the active avoidance response rate and the total avoidance response rate were decreased. The number of NeuN positive cells decreased and the expression levels of GLUT1 and GLUT3 genes and proteins were decreased(P<0. 05). Compared with the aging model group, the escape latency significantly declined(P<0. 01), but the rates of active avoidance response and total avoidance response increased, the number of NeuN positive cells increased significantly, the expression levels of GLUT1 and GLUT3 genes and proteins up-regulated in the rats of the three intervention groups(P<0. 05 or P<0. 01). Compared with the soy isoflavones group, the active avoidance response rate was increased in the combined group(P<0. 05). In comparison with those for the resveratrol group, the avoidance latency was shortened and the active avoidance response rate was increased, the number of NeuN positive cells and the expression levels of GLUT3 gene and protein were significantly increased in the combined group(P<0. 05). There was no significant difference between the combined intervention group and the estradiol valerate group(P>0. 05).

CONCLUSION

Resveratrol and soy isoflavones alone and in combination can improve the learning and memory ability of aging rat models. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes and proteins in the hippocampus, promoting the transmembrane transport of glucose and reducing neuronal loss.

摘要

目的

探讨白藜芦醇联合大豆异黄酮对衰老模型大鼠回避记忆、神经元特异性核蛋白(NeuN)阳性细胞数量及海马中葡萄糖转运蛋白(GLUT)1和GLUT3表达的影响。

方法

将60只雌性SD大鼠随机分为6组,包括假手术对照组、衰老模型组、80mg/kg白藜芦醇组、160mg/kg大豆异黄酮组、80mg/kg白藜芦醇+160mg/kg大豆异黄酮组、0.8mg/kg戊酸雌二醇组。采用卵巢切除联合腹腔注射100mg/kg D-半乳糖诱导衰老模型大鼠。每天灌胃给药1次,连续12周。通过穿梭箱试验测量回避任务。采用免疫荧光法检测NeuN表达。分别通过实时荧光定量PCR和蛋白质印迹法检测大鼠海马中GLUT1和GLUT3的基因和蛋白表达。

结果

与假手术对照组相比,衰老模型组的回避潜伏期延长,主动回避反应率和总回避反应率降低。NeuN阳性细胞数量减少,GLUT1和GLUT3基因及蛋白表达水平降低(P<0.05)。与衰老模型组相比,三个干预组大鼠的逃避潜伏期显著缩短(P<0.01),但主动回避反应率和总回避反应率升高,NeuN阳性细胞数量显著增加,GLUT1和GLUT3基因及蛋白表达水平上调(P<0.05或P<0.01)。与大豆异黄酮组相比,联合组的主动回避反应率升高(P<0.05)。与白藜芦醇组相比,联合组的回避潜伏期缩短,主动回避反应率升高,NeuN阳性细胞数量及GLUT3基因和蛋白表达水平显著增加(P<0.05)。联合干预组与戊酸雌二醇组之间无显著差异(P>0.05)。

结论

白藜芦醇和大豆异黄酮单独及联合应用均可改善衰老模型大鼠的学习记忆能力。其机制可能与上调海马中GLUT1和GLUT3基因及蛋白表达、促进葡萄糖跨膜转运和减少神经元丢失有关。

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