黄芩甙对慢性脑低灌注大鼠认知功能及其对海马内LC-3Ⅱ和Beclin-1表达的影响

doi:10.3969/j.issn.1006-7795.2019.03.002

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (3): 330-334.doi: 10.3969/j.issn.1006-7795.2019.03.002

黄芩甙对慢性脑低灌注大鼠认知功能及其对海马内LC-3Ⅱ和Beclin-1表达的影响

陈玉静¹, 陈文强¹, 张建新², 刘妍¹, 吴犀翎¹, 王建东¹, 黄小波¹

1. 首都医科大学宣武医院中医科, 北京市中西医结合老年疾病研究所, 北京 100053;
2. 山东省夏津县人民医院内科, 山东德州 253200

收稿日期:2018-12-06 出版日期:2019-05-21 发布日期:2019-06-13
通讯作者: 黄小波 E-mail:huangxiaobo@ccmu.edu.cn
基金资助:
国家自然科学基金（81574936），北京市自然科学基金（7162079，7172094），北京市中医药科技项目（JJ2018-22）。

Effects of baicalin on cognitive function and expression of LC-3Ⅱ and Beclin-1 proteins in hippocampus of rats with chronic cerebral hypoperfusion

Chen Yujing¹, Chen Wenqiang¹, Zhang Jianxin², Liu Yan¹, Wu Xiling¹, Wang Jiandong¹, Huang Xiaobo¹

1. Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University;Beijing Institute of Geriatric Diseases with Integrated Traditional Chinese and Western Medicine, Beijing 100053, China;
2. Department of Internal Medicine, Xiajin People's Hospital, Shandong Province, Dezhou 253200, Shandong Province, China

Received:2018-12-06 Online:2019-05-21 Published:2019-06-13
Supported by:
This study was supported by National Natural Science Foundation of China (81574936), Natural Science Foundation of Beijing (7162079,7172094), Beijing Traditional Chinese Medicine Science and Technology Project (JJ2018-22).

摘要/Abstract

摘要： 目的观察黄芩甙对慢性脑低灌注大鼠学习记忆功能及海马区自噬相关蛋白LC-3Ⅱ和Beclin-1表达的影响。方法将50只SD大鼠按随机数字表法分为对照组、模型组和黄芩甙低、中、高剂量组，每组各10只。采用永久性双侧颈总动脉结扎建立慢性脑低灌注大鼠模型，黄芩甙组腹腔注射3种不同剂量的黄芩甙（60、120、240 mg·kg^-1·d^-1），对照组和模型组给予等量0.9%（质量分数）氯化钠注射液腹腔注射。4周后采用Morris水迷宫法进行行为学检测，Western blotting法检测自噬相关蛋白LC-3Ⅱ和Beclin-1的表达。结果与对照组相比，模型组Morris水迷宫平均逃避潜伏期和游泳距离均明显延长（P<0.01），空间探索实验中在原平台所在象限游泳时间明显缩短（P<0.01），海马区自噬相关蛋白LC-3Ⅱ和Beclin-1表达明显增加（P<0.01）。与模型组比较，黄芩甙干预后，大鼠学习记忆能力显著改善（P<0.01或P<0.05），海马内LC-3Ⅱ和Beclin-1表达均显著低于模型组（P<0.01或P<0.05），差异有统计学意义。结论黄芩甙能够改善慢性脑低灌注大鼠的学习记忆功能，并抑制自噬相关蛋白LC-3Ⅱ和Beclin-1的表达。

关键词: 黄芩甙, 慢性脑低灌注, 认知功能, 自噬

Abstract: Objective To investigate the effects of baicalin on the cognitive ability and the expression of LC-3 Ⅱ and Beclin-1 proteins in hippocampus of the rats with chronic cerebral hypoperfusion. Methods A total of 50 rats were randomly divided into five groups:control group, model group, low,medium, and high dose of baicalin groups with 10 rats in each group. The chronic cerebral hypoperfusion rat model was established by permanent bilateral common carotid artery occlusion.Baicalin groups were treated with intraperitoneal injection of baicalin in three different dosages (60,120,240 mg·kg^-1·d^-1), while those in the other two groups were treated with the same volume of saline. After four weeks, the spatial learning and memory ability were observed by Morris water maze test, and the expression of LC-3 Ⅱ and Beclin-1 in the hippocampus were revealed with Western blotting.Results Both escape latency and swimming distance of the chronic cerebral hypoperfusion rats were significantly prolonged in comparison of those in normal control (P<0.01), and swimming time in the platform of previous quadrant was significantly shorter in model group (P<0.01). Furthermore, the expression of LC-3 Ⅱ and Beclin-1 protein increased in model group compared with the control group (P<0.01). Four weeks of treatment with baicalin remarkably improved the learning and memory ability of chronic cerebral hypoperfusion rats (P<0.01 or P<0.05), decreased the expression of LC-3 Ⅱ and Beclin-1 in hippocampus of the model rats (P<0.01 or P<0.05). Conclusion Baicalin can improve cognitive ability of the chronic cerebral hypoperfusion rats, and inhibit autophagy by decreasing the expression of LC-3 Ⅱ and Beclin-1 in the hippocampus.

Key words: baicalin, chronic cerebral hypoperfusion, cognitive ability, autophagy

中图分类号:

R255.4

陈玉静, 陈文强, 张建新, 刘妍, 吴犀翎, 王建东, 黄小波. 黄芩甙对慢性脑低灌注大鼠认知功能及其对海马内LC-3Ⅱ和Beclin-1表达的影响[J]. 首都医科大学学报, 2019, 40(3): 330-334.

Chen Yujing, Chen Wenqiang, Zhang Jianxin, Liu Yan, Wu Xiling, Wang Jiandong, Huang Xiaobo. Effects of baicalin on cognitive function and expression of LC-3Ⅱ and Beclin-1 proteins in hippocampus of rats with chronic cerebral hypoperfusion[J]. Journal of Capital Medical University, 2019, 40(3): 330-334.

参考文献

[1] Duncombe J, Kitamura A, Hase Y, et al. Chronic cerebral hypoperfusion:a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia[J]. Clin Sci (Lond),2017, 131(19):2451-2468.
[2] Hamano T, Hayashi K, Shirafuji N, et al. The implications of autophagy in alzheimer's disease[J]. Curr Alzheimer Res, 2018, 15(14):1283-1296.
[3] Liang W, Huang X, Chen W. The effects of baicalin and baicalein on cerebral ischemia:a review[J]. Aging Dis,2017, 8(6):850-867.
[4] Chen C, Li X, Gao P, et al. Baicalin attenuates alzheimER-like pathological changes and memory deficits induced by amyloid β1-42 protein[J]. Metab Brain Dis, 2015, 30(2):537-544.
[5] Wang Z,Fan J,Wang J,et al,Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats[J].Behav Brain Res,2016, 301:243-252.
[6] Morris R. Developments of a water maze procedure for studying spatial learning in the rat[J]. J Neurosci Methods, 1984, 11(1):47-60.
[7] Iadecola C. The pathobiology of vascular dementia[J].Neuron, 2013, 80(4):844-866.
[8] Zhao Y, Gong C X. From chronic cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration[J].Cell Mol Neurobiol,2015,35(1):101-110.
[9] Kim S, Kang I H, Nam J B, et al. Ameliorating the effect of astragaloside Ⅳ on learning and memory deficit after chronic cerebral hypoperfusion in rats[J]. Molecules, 2015, 20(2):1904-1921.
[10] Jing Z, Shi C, Zhu L, et al. Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but also neuronal degeneration and cognitive impairment[J]. J Cereb Blood Flow Metab, 2015, 35(8):1249-1259.
[11] Wang D, Kiesinger P R. Autophagy, neuron-specific degradation and neurodegeneration[J]. Autophagy, 2012, 8(4):711-713.
[12] Kang R, Zeh H J, Lotze M T, et al. The beclin 1 network regulates autophagy and apoptosis[J]. Cell Death Differ, 2011, 18(4):571-580.
[13] Klionsky D J, Abdalla F C, Abeliovich H, et al. Guidelines for the use and interpretation of assays for monitoring autophagy[J]. Autophagy, 2012, 8(4):445-544.
[14] Ghavami S, Cunnington R H, Yeganeh B, et al. Autophagy regulates trans fatty acid-mediated apoptosis in primary cardiac my fibroblasts[J]. Biochim Biophys Acta, 2012, 1823(12):2274-2286.
[15] Gong C, Bauvy C, Tonelli G, et al. Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells[J].Oncogene, 2013, 32(18):2261-2272.
[16] Dou Z, Xu C, Donahue G, et al. Autophagy mediates degradation of nuclear lamina[J]. Nature, 2015,527(7576):105-109.
[17] 邹文颖, 李玉梅, 付剑亮. 慢性脑低灌注所致认知障碍大鼠海马区自噬机制的初步研究[J]. 中国临床神经科学,2016, 24(1):33-41.
[18] Ohta K, Mizuno A, Ueda M, et al. Autophagy impairment stimulates PS1 expression and gamma-secretase activity[J]. Autophagy, 2010, 6(3):345-352.
[19] 徐昕, 颜小华. 黄芩苷治疗脑损伤的研究进展[J].实用临床医学, 2012, 13(8):131-136.
[20] Chen C, Li X H, Gao P L, et al. Baicalin attenuates Alzheimer-like pathological changes and memory deficits induced by amyloid β1-42 protein[J]. Metab Brain Dis, 2015, 30(2):537-544.
[21] Zhao J W, Lu S, Yu H, et al. Baicalin and ginsenoside Rb1 promote the proliferation and differentiation of neural stem cells in Alzheimer's disease model rats[J]. Brain Res, 2018, 1678:187-194.

黄芩甙对慢性脑低灌注大鼠认知功能及其对海马内LC-3Ⅱ和Beclin-1表达的影响

Effects of baicalin on cognitive function and expression of LC-3Ⅱ and Beclin-1 proteins in hippocampus of rats with chronic cerebral hypoperfusion

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	李琼, 赵建华, 刘昊, 王凡, 李青, 陈希妍, 蔡瑞艳, 吴清武, 张健, 吉四辈, 路承彪, 李少敏. 脑白质高信号患者血清CX3CL1水平与认知功能障碍的关系[J]. 首都医科大学学报, 2023, 44(1): 6-12.
[2]	王梦迪, 郭弋凡, 庞彦余, 刘羽飞, 赵文景. 保肾通络方含药血清调节线粒体自噬对高糖诱导下足细胞氧化损伤的影响[J]. 首都医科大学学报, 2022, 43(5): 687-693.
[3]	安宇, 边南南, 丁小雨, 常晓娜, 刘佳, 王广. 1型糖尿病伴认知功能损伤小鼠脑组织肠道菌群代谢物的改变[J]. 首都医科大学学报, 2022, 43(4): 622-629.
[4]	许新, 阮祥燕, 鞠蕊, 杨瑜, 程姣姣, 王志坤, Alfred O. Mueck. 中国女性轻度认知障碍的影响因素及其与绝经症状的关系[J]. 首都医科大学学报, 2022, 43(3): 369-374.
[5]	任艳萍, 张俊岩, 吴涵, 罗炯, 杨春林, 马辛, 姜玮. 磁惊厥治疗与无抽搐电痉挛治疗抑郁发作的早期疗效及对认知功能的影响[J]. 首都医科大学学报, 2022, 43(2): 239-243.
[6]	杨柳青, 田红梅, 石汉平. 三种饮食模式与慢性疾病研究进展[J]. 首都医科大学学报, 2022, 43(2): 311-320.
[7]	刘志斌, 靳松, 牛亦农. 苯乙基异硫氰酸酯对良性前列腺上皮细胞增殖凋亡的影响及相关机制研究[J]. 首都医科大学学报, 2021, 42(6): 961-966.
[8]	李志, 张郡, 戴悦萱, 秦明阳, 梁芙茹. 血糖波动对2型糖尿病大鼠认知功能的影响[J]. 首都医科大学学报, 2021, 42(3): 347-353.
[9]	郝淑文, 陈瑛, 丁晖, 赵春松, 梁阔, 薛金花, 蔡彦宁. 阿尔茨海默病、轻度认知功能障碍及主观认知下降患者血液DNA中多个基因的甲基化分析[J]. 首都医科大学学报, 2021, 42(3): 447-452.
[10]	杨楠, 丁锚, 闫峰, 师文娟, 黄语悠, 赵咏梅. 远隔缺血预适应对脑缺血再灌注损伤大鼠缺血半暗带区PERK/p-eIF2α通路及自噬的影响[J]. 首都医科大学学报, 2021, 42(2): 225-231.
[11]	张颖, 王若梅, 李刚. 稳定期精神分裂症患者认知功能、情绪管理水平及其影响因素分析[J]. 首都医科大学学报, 2021, 42(1): 143-147.
[12]	崔兴, 钟萍. 我的梦想是做“百年老店”——记首都医科大学三博脑科医院神经外科于春江教授[J]. 首都医科大学学报, 2021, 42(1): 167-169.
[13]	王明洋, 孙争宇, 张丽, 李雅莉, 李林, 张兰. 山茱萸环烯醚萜苷对脑缺血再灌注大鼠线粒体损伤的影响[J]. 首都医科大学学报, 2020, 41(3): 385-390.
[14]	吴凤芝, 宁艳哲, 贾竑晓. 脾虚证患者认知功能的临床特征[J]. 首都医科大学学报, 2020, 41(1): 55-58.
[15]	宋楠, 贾竑晓. 人格解体患者认知功能及与临床症状和社会功能的相关性[J]. 首都医科大学学报, 2020, 41(1): 59-63.