食品科学 ›› 2019, Vol. 40 ›› Issue (15): 162-168.doi: 10.7506/spkx1002-6630-20180728-349

• 营养卫生 • 上一篇    下一篇

白藜芦醇对衰老小鼠脑神经细胞的保护机制

张贤益,宋也好,李 露,尹术华,付王威,吴睿婷,潘 猛,吴文英,汤小芳,李文娟   

  1. 南昌大学 食品科学与技术国家重点实验室,江西 南昌 330047
  • 出版日期:2019-08-15 发布日期:2019-08-26
  • 基金资助:
    国家自然科学基金地区科学基金项目(31560460);江西省自然科学基金重点项目(20171ACB21016);南昌大学研究生创新专项资金项目(CX2017134)

Protective Effect and Mechanism of Resveratrol on Cerebral Nerve Cells of Aging Mice

ZHANG Xianyi, SONG Yehao, LI Lu, YIN Shuhua, FU Wangwei, WU Ruiting, PAN Meng, WU Wenying, TANG Xiaofang, LI Wenjuan   

  1. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
  • Online:2019-08-15 Published:2019-08-26

摘要: 目的:探究白藜芦醇(resveratrol,RSV)对D-半乳糖(D-galactose,D-gal)致衰老小鼠脑神经细胞的保护机制。方法:采用腹腔注射D-gal建立小鼠亚急性衰老模型;检测其体质量、脑器官指数、记忆能力变化;用流式细胞仪检测脑神经细胞的凋亡率、活性氧(reactive oxygen species,ROS)水平、线粒体膜电位(mitochondrial membrane potential,MMP)变化;测定线粒体Caspase-9和Caspase-3的活力;采用Western blotting法检测线粒体细胞色素c(cytochrome c,Cyt c)、胞浆Cyt c的表达差异。结果:实验周期内各组间小鼠体质量均无显著变化(P>0.05);而与对照组相比,D-gal组小鼠脑器官指数显著减小(P<0.05),穿越隐藏平台次数减少,脑神经细胞凋亡率极显著升高(P<0.01),表明D-gal对小鼠脑神经细胞造成明显损伤。与D-gal组相比,RSV处理组小鼠脑器官指数均上升,其中D-gal+RSV(25)组效果最明显(P<0.05);穿越隐藏平台次数均有增加,但无显著性差异(P>0.05);神经细胞凋亡率均极显著降低(P<0.01),表明RSV对D-gal致衰老小鼠脑神经细胞具有保护作用。与Control组相比,D-gal组小鼠脑神经细胞ROS水平极显著升高(P<0.01),MMP极显著降低(P<0.01),Caspase-9和Caspase-3活力极显著上升(P<0.01),线粒体Cyt c表达下降、胞浆Cyt c表达增加,表明D-gal对小鼠线粒体功能造成损伤;而与D-gal组相比,RSV处理组小鼠脑神经细胞ROS水平均极显著下降(P<0.01),MMP均极显著升高(P<0.01),Caspase-9和Caspase-3活力均极显著降低(P<0.01),线粒体Cyt c表达显著上升(P<0.05),胞浆Cyt c表达显著降低(P<0.05)。结论:RSV能通过线粒体通路对D-gal致衰老小鼠脑神经细胞产生保护作用。

关键词: 白藜芦醇, D-半乳糖, 细胞凋亡, 神经保护, 线粒体通路

Abstract: Objective: To investigate the protective effect and underlying mechanism of resveratrol (RSV) on cerebral nerve cells in aging mice induced by D-galactose (D-gal). Methods: An aging mouse model was established by intraperitoneal injection of D-gal. The changes in body mass and brain index (brain/body mass ratio) were calculated. Apoptotic rate, reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) in cerebral cortical neurons were measured by flow cytometry. Mitochondrial caspase-9 and caspase-3 activity were measured, and the difference in the expression of mitochondrial and cytoplasmic cytochrome c (Cyt c) was analyzed by Western blotting. Results: There was no significant difference in body mass among all groups within the experimental period (P > 0.05). Brain index decreased significantly in the aging model group (P < 0.05), the number of times the mice crossed the hidden platform declined and the apoptotic rate of neurons significantly increased (P < 0.01) compared with the normal group, indicating that D-gal significantly damaged nerve cells in mice. Brain index in all three RSV treatment groups especially at a dose of 25.00 mg/kg mb was significantly higher than in the model group (P < 0.01), the number of times the mice crossed the hidden platform increased but with no significance (P > 0.05), and the apoptotic rate of nerve cells declined significantly (P < 0.01), leading to the conclusion that RSV has a protective effect on cerebral neural cells of D-gal-induced aging mice. ROS content in nerve cells of the model group increased significantly (P < 0.01), and MMP significantly decreased compared with the normal group (P < 0.01). Moreover, the expression of mitochondrial Cyt c decreased, the expression of cytoplasmic Cyt c increased, and mitochondrial caspase-9 and caspase-3 activity increased significantly in the model group (P < 0.01), indicating that D-gal could lead to mitochondrial damage. Compared with the model group, ROS level in nerve cells significantly decreased in the RSV groups (P < 0.01); MMP significantly increased (P < 0.01); the expression of mitochondrial Cyt c significantly increased, while the expression of cytoplasmic Cyt c significantly decreased (P < 0.05); and the activity of caspase-9 and caspase-3 significantly decreased (P < 0.01), indicating that resveratrol exerts its protective effect on nerve cells of aging mice through the mitochondrial pathways. Conclusion: Resveratrol can protect cerebral nerve cells of aging mice induced by D-gal through the mitochondrial pathways.

Key words: resveratrol, D-galactose, apoptosis, neuroprotection, mitochondrial pathway

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