白肉灵芝水提物改善衰老大鼠认知功能的作用

王昱

doi:10.16098/j.issn.0529-1356.2022.06.004

PDF(11922 KB)

解剖学报 ›› 2022, Vol. 53 ›› Issue (6) : 711-718. DOI: 10.16098/j.issn.0529-1356.2022.06.004

神经生物学

白肉灵芝水提物改善衰老大鼠认知功能的作用

王昱^1,2*秦序^1,2何九军^1,2王逸璇³

作者信息 +

Effect of the aqueous extracts of ganoderma leucocontextum on cognitive function of aging rats

WANG Yu^1,2* QIN Xu^1,2 HE Jiu-jun^1,2 WANG Yi-xuan³

Author information +

文章历史 +

摘要

目的探讨白肉灵芝水提物（GLAE）改善衰老大鼠认知功能的作用及机制。方法将50只健康大鼠分成对照组、模型组、GLAE低剂量组、GLAE中剂量组和GLAE高剂量组，用D-半乳糖构建衰老SD大鼠模型，同时分别给予不同剂量的（0、50、100 和200 mg/kg）GLAE处理，采用新物体认知和跳台实验方法检测大鼠认知功能的改变，甲苯胺蓝、吉姆萨和HE染色进行病理学观察，彗星电泳检测大脑细胞DNA的损伤，ELISA、Western blotting和Real-time PCR法检测大脑组织蛋白激酶A（PKA）/环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）信号通路相关因子表达。结果与模型组比较，GLAE干预后，大鼠认知功能衰退及大脑皮层病理变化有显著改善，大脑细胞DNA损伤程度显著降低（P<0.05），大脑组织cAMP、脑源性神经生长因子（BDNF）和神经生长因子（NGF）含量显著增高（P<0.01，P<0.05），PKA、BDNF、NGF和CREB mRNA及PKA、BDNF、NGF和CREB蛋白的表达水平显著上升（P<0.01，P<0.05）。结论 GLAE可改善衰老大鼠的认知功能，其机制可能与其激活大脑PKA/CREB信号通路，增加神经营养因子含量，抑制大脑细胞DNA损伤有关。

Abstract

Objective To investigate the effects of the aqueous extracts of ganoderma leucocontextum (GLAE) on cognitive decline of aging rats and possible regulation mechanism. Methods Fifty rats were divided into five groups, control group, model group, GLAE low-dose group, GLAE middle-dose group and GLAE high-dose group. Aging SD rat models were made by D-galactose, and then treated continuously with different doses (0, 50, 100, 200 mg/kg) of GLAE. The novel object recognition and step down test were performed to detect the changes of rats cognitive function. The brain tissue was stained with toluidine blue, Giemsa and HE staining and observed. The cerebral cell DNA damage was detected by comet assay. Expressions of protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) signaling pathway related factors in brain were respectively detected by ELISA, Western blotting and Real-time PCR. Results Compared with the model group, administration of GLAE could obviously alleviate rats cognitive decline and pathological change. The levels of cell DNA damage reduced markedly (P<0.05). The contents of cAMP, brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), and also expression levels of mRNA and protein of PKA, BDNF, NGF, CREB in the brain increased significantly in each medicated group (P<0.01, P<0.05). Conclusion GLAE can improve cognitive function, and its mechanism may be related to activation of brain PKA/CREB signaling pathway, increase in neurotrophic factor content and inhibition of cell DNA damage.

导出引用

王昱秦序何九军王逸璇. 白肉灵芝水提物改善衰老大鼠认知功能的作用[J]. 解剖学报. 2022, 53(6): 711-718 https://doi.org/10.16098/j.issn.0529-1356.2022.06.004

WANG Yu QIN Xu HE Jiu-jun WANG Yi-xuan. Effect of the aqueous extracts of ganoderma leucocontextum on cognitive function of aging rats [J]. Acta Anatomica Sinica. 2022, 53(6): 711-718 https://doi.org/10.16098/j.issn.0529-1356.2022.06.004

中图分类号： R741

参考文献

［1］Li TH, Hu HP, Deng WQ, et al. Ganoderma leucocontextum, a new member of the G. lucidum complex from southwestern China ［J］. Mycoscience, 2015, 56: 81-85.

［2］Xiong Ch, Chen Ch, Chen ZQ, et al. Potentiation of neuritogenic activity of Ganoderma leucocontextum on rat pheochromocytoma cells［J］.Natural Product Research and Development,2016,28(7): 1135-1138(in Chinese)

熊川, 陈诚, 陈祖琴, 等. 白肉灵芝水提物促进 PC-12细胞分化作用研究［J］. 天然产物研究与开发, 2016, 28(7): 1135-1138.

［3］Xiong Ch, Chen Ch, Huang WL, et al. Protective effects of aqueous extracts of ganoderma leucocontextum on H2O2 induced apopotosis in PC12 cells［J］.Journal of Food Safety and Quality, 2016,7(2):662-668.(in Chinese)

熊川, 陈诚, 黄文丽, 等. 白肉灵芝水提物对 H2O2诱导PC-12 细胞凋亡的保护作用［J］. 食品安全质量检测学报, 2016,7(2): 662-668.

［4］Wang Y, He JJ, Zhang ZZh. Effect of the aqueous extracts of ganoderma leucocontextum on aging rats skin［J］. Nat Prod Res Dev, 2019, 31(12): 2131-2136. (in Chinese)

王昱, 何九军, 张宗舟.白肉灵芝水提物对衰老大鼠皮肤的作用研究［J］. 天然产物研究与开发, 2019, 31(12): 2131-2136.

［5］Gao H, Yan P, Zhang S, et al. Long-term dietary alpha-linolenic acid supplement alleviates cognitive impairment correlatewith activating hippocampal CREB signaling in natural aging rats［J］. Mol Neurobiol, 2016, 53(7): 4772-4781.

［6］Sun HL, Wu H, Liu J, et al. Prenatal stress impairs spatial learning and memory associated with lower mRNA level of the CAMKII and CREB in the adult female rat hippocampus［J］. Neurochem Res, 2017, 42 (5): 1496-1503.

［7］Stepanichev M, Onufriev M, Aniol V, et al. Effects of cerebrolysin on nerve growth factor system in the aging rat brain［J］. Restor Neurol Neuros, 2017, 35(6): 571-581.

［8］Molinari C, Morsanuto V, Rugas S, et al. The role of BDNF on aging-modulation markers［J］. Brain Sci, 2020, 10(5): 285-294.

［9］Song J, Pang YY, Gao L, et al. Effects of scutellaria baicalensis georgi flowers on D-galactose induced aging in rats based on serum metabolomics［J］. Acta Pharmaceutica Sinica,2019, 54(3): 533-539. (in Chinese)

宋佳, 庞溢媛, 高丽, 等. 基于血清代谢组学的黄芩花干预D-半乳糖致衰老大鼠作用研究［J］. 药学学报, 2019, 54(3): 533-539.

［10］Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates ［M］. 5th ed. San Diego: Academic Press, 2009：50-115.

［11］Wang YCh, Yu ShY, Wang Y, et al. Effects of X-ray on the structure of cerebral temporal lobe cortex and activity of acetylcholinesterase and expression of Bax and epidermal growth factor of filial mice［J］. Acta Anatomica Sinica, 2011, 42(3): 307-313. (in Chinese)

王元春, 俞诗源, 王昱, 等. X线辐射对仔鼠大脑颞叶皮层结构及乙酰胆碱酯酶活性、Bax蛋白和表皮生长因子表达的影响［J］. 解剖学报, 2011, 42(3): 307-313.

［12］Wang Y, Li ChY, Yu ShY, et al. Effects on the structure of cerebral temporal lobe cortex and capability of learning and memory of filial mice after administration of heroin and ephedrine［J］. Acta Anatomica Sinica, 2009, 40(5): 724-731. (in Chinese)

王昱, 李重阳, 俞诗源, 等. 注射海洛因、麻黄素对仔鼠大脑颞叶皮层结构及学习记忆能力的影响［J］. 解剖学杂志, 2009, 40(5): 724-731.

［13］Ding RC, Ji K, Wu DN, et al. Effect of modified ditan decoction on behavior and PKA/CREB signaling pathway in vascular dementia rats［J］. Chinese Journal of Integrated Traditional and Western Medicine, 2020, 21(1): 17-20. (in Chinese)

丁瑞丛, 纪可, 吴东南, 等. 涤痰汤加味方对血管性痴呆大鼠行为学及PKA/CREB 信号通路的影响［J］. 中国中西医结合杂志, 2020, 21(1): 17-20.

［14］Raghunathan R, Hogan JD, Labadorf A, et al. A glycomics and proteomics study of aging and parkinson’s disease in human brain［J］. Scientific Reports, 2020, 10(1): 1277-1340.

［15］Cortes-canteli M, Iadecola C. Alzheimer’s disease and vascular aging ［J］. J Am Coll Cardiol, 2020, 75(8): 942-951.

［16］Emily M, Amber LS. Biological aging and the cellular pathogenesis of huntington’s disease ［J］. J Huntington’s Disease, 2020, 9(6): 1-14.

［17］Shen Y, Gao X, Qin YQ, et al. Flavored sijunzi delays aging of brain tissue of mice via mTOR signaling pathway［J］. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2018, 47(4): 417-420. (in Chinese)

沈莹, 高啸, 覃艳琼, 等. 加味四君子汤通过mTOR信号通路延缓小鼠脑组织衰老的机制研究［J］. 华中科技大学学报(医学版), 2018, 47(4): 417-420.

［18］Grootaert MOJ, Manon M, Lynn R, et al. Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis ［J］. Cardiovasc Res, 2018, 114(4): 622-634.

［19］Li X, Wang L, Zhang SL, et al. Timing-dependent protection of swimming exercise against D-galactose-induced aging-like impairments in spatial learning/memory in rats［J］. Brain Sci, 2019, 9(9): 236-245.

［20］Ma CL, Li L, Yang GM, et al. Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron［J］. Hum Exp Toxicol, 2020, 39(8): 1118-1129.

［21］Li X, Guo C, Li Y, et al. Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway［J］. Oncotarget, 2017, 8(20): 32433-32449.

［22］Li YM, Zhang WN, Shi RX, et al. Prenatal caffeine damaged learning and memory in rat offspring mediated by ARs/PKA/CREB/BDNF pathway ［J］. Physiol Res, 2018, 67(6): 975-983.

［23］Du Q, Zhu XY, Si J, et al. Angelica polysaccharide ameliorates memory impairment in Alzheimer’s disease rat through activating BDNF/TrkB/CREB pathway［J］. Exp Biol Med, 2020, 245(1): 1-10.

［24］Wang ChY, Guo JY, Guo RJ. Effect of XingPiJieYu decoction on spatial learning and memory and cAMPPKACREBBDNF pathway in rat model of depression through chronic unpredictable stress［J］. BMC Complement Med Ther, 2017, 17(1): 73-82.