

浏览全部资源
扫码关注微信
1.南京中医药大学 针灸推拿学院,养生康复学院,南京 210023
2.南京大学医学院 附属鼓楼医院,南京 210008
3.南京中医药大学 国际经方学院,南京 210023
4.南京中医药大学 附属医院,南京 210029
5.南京中医药大学 鼓楼临床医学院,南京 210008
6.School of Pharmacy,Management and Science University,Shah Alam 40100,Malaysia
Received:30 April 2021,
Published Online:20 July 2021,
Published:20 September 2021
移动端阅览
涂玥,倪光夏,万毅刚等.经典名方及其有效成分调节免疫衰老的作用机制研究进展[J].中国实验方剂学杂志,2021,27(18):190-197.
TU Yue,NI Guang-xia,WAN Yi-gang,et al.Mechanisms of Classical Prescriptions and Their Active Components in Immunosenescence Regulation: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(18):190-197.
涂玥,倪光夏,万毅刚等.经典名方及其有效成分调节免疫衰老的作用机制研究进展[J].中国实验方剂学杂志,2021,27(18):190-197. DOI: 10.13422/j.cnki.syfjx.20211705.
TU Yue,NI Guang-xia,WAN Yi-gang,et al.Mechanisms of Classical Prescriptions and Their Active Components in Immunosenescence Regulation: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(18):190-197. DOI: 10.13422/j.cnki.syfjx.20211705.
伴随着机体衰老,免疫系统会发生一系列变化。这一类衰老相关性免疫系统改变被称为“免疫衰老”,其病变主要表现在细胞免疫上。研究表明,参与调节免疫衰老的免疫细胞包括固有免疫细胞和适应免疫细胞,前者包括“中性粒细胞、单核/巨噬细胞、髓样抑制细胞、树突状细胞及自然杀伤细胞”等,其作用机制涉及细胞数量、吞噬能力、趋化性、黏附力及Toll样受体(TLR)功能、抗原提呈能力、巨噬细胞极化、细胞毒性、迁移能力等;后者包括“T淋巴细胞和B淋巴细胞”等,其作用机制涉及细胞发育、增殖、分化能力、细胞数量、端粒酶活性、自身反应性抗体等。免疫衰老不仅是机体衰老的体现,更是中、西药物延缓衰老的重要靶标。近年来,国内外中医药学者相继发现一些经典名方(简称“经方”)及其有效成分,如独参汤及其有效成分人参叶总皂苷、生脉饮及其有效成分安五脂素、人参茎叶总皂苷等,能够靶向免疫细胞,干预其分子调控机制,进而发挥调节免疫衰老的作用。此外,经方调节免疫衰老还与自噬密切相关。“祛瘀生新法”代表性经方——大黄䗪虫丸能延缓
D
-半乳糖诱导的小鼠肾脏衰老,其作用机制不仅在于调节胸腺免疫细胞数量和活性,还能改善肾脏中自噬标志性蛋白和炎症性细胞因子的表达。因此,“基于免疫衰老的作用机制探究经方及其有效成分的干预效果”将会成为抗衰老药物研究和开发的新方向。
As the body ages, the immune system will undergo a series of changes, which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils, monocytes/macrophages, myeloid-derived suppressor cells, dendritic cells, natural killer cells, etc., and the underlying mechanisms involve the regulation of cell number, phagocytosis, chemotaxis, adhesion, the function of toll-like receptor (TLR), antigen presentation, macrophage polarization, cytotoxicity, migration, etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes, and the underlying mechanisms involve the regulation of cell development, proliferation, differentiation, cell number, telomerase activity, self-reactive antibodies, etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years, scholars have found some classical prescriptions and their active components (such as Dushentang and total saponins in
Panax ginseng
leaves, and Shengmaiyin and anwulignan and total saponins in
P. ginseng
stems and leaves) can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition, the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration, Dahuang Zhechongwan, can delay
D
-galactose-induced renal aging in mice, and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore, exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.
XU W , WONG G , HWANG Y Y , et al . The untwining of immunosenescence and aging [J]. Semin Immunopathol , 2020 , 42 ( 5 ): 559 - 572 .
GOODELL M A , RANDO T A . Stem cells and healthy aging [J]. Science , 2015 , 350 ( 6265 ): 1199 - 1204 .
BARBÉ-TUANA F , FUNCHAL G , SCHMITZ C R R , et al . The interplay between immunosenescence and age-related diseases [J]. Semin Immunopathol , 2020 , 42 ( 5 ): 545 - 557 .
MULDER W J M , OCHANDO J , JOOSTEN L A B , et al . Therapeutic targeting of trained immunity [J]. Nat Rev Drug Discov , 2019 , 18 ( 7 ): 553 - 566 .
YOUSEFZADEH M J , FLORES R R , ZHU Y , et al . An aged immune system drives senescence and ageing of solid organs [J]. Nature , 2021 , 594 ( 7861 ): 100 - 105 .
URSINI F , RUSSO E , PELLINO G , et al . Metformin and autoimmunity:a "new deal" of an old drug [J]. Front Immunol , 2018 , 9 : 1236 .
ROSTAMZADEH D , YOUSEFI M , HAGHSHENAS M R , et al . mTOR Signaling pathway as a master regulator of memory CD8 + T-cells,Th17,and NK cells development and their functional properties [J]. J Cell Physiol , 2019 , 234 ( 8 ): 12353 - 12368 .
LIU Z B , YANG J P , XU L R . Effectiveness and safety of traditional Chinese medicine in treating acquired immune deficiency syndrome:2004-2014 [J]. Infect Dis Poverty , 2015 , 4 : 59 .
MA H D , DENG Y R , TIAN Z , et al . Traditional Chinese medicine and immune regulation [J]. Clin Rev Allergy Immunol , 2013 , 44 ( 3 ): 229 - 241 .
JACKAMAN C , TOMAY F , DUONG L , et al . Aging and cancer:the role of macrophages and neutrophils [J]. Ageing Res Rev , 2017 , 36 : 105 - 116 .
DREW W , WILSON D V , SAPEY E . Inflammation and neutrophil immunosenescence in health and disease:targeted treatments to improve clinical outcomes in the elderly [J]. Exp Gerontol , 2018 , 105 : 70 - 77 .
TSENG C W , LIU G Y . Expanding roles of neutrophils in aging hosts [J]. Curr Opin Immunol , 2014 , 29 : 43 - 48 .
JUTHANI-MEHTA M , GUO X , SHAW A C , et al . Innate immune responses in the neutrophils of community dwelling and nursing home elders [J]. J Aging Sci , 2014 , 2 : 1000115 .
黄煌 . 黄煌经方使用手册 [M]. 4版 . 北京 : 中国中医药出版社 , 2020 .
黄煌 . 黄煌经方基层医生读本 [M]. 北京 : 中国中医药出版社 , 2020 .
WEI G , DONG L , YANG J , et al . Integrated metabolomic and transcriptomic analyses revealed the distribution of saponins in Panax notoginseng [J]. Acta Pharm Sin B , 2018 , 8 ( 3 ): 458 - 465 .
张克坚 , 刘耕陶 . 人参叶总皂甙对老龄大鼠白细胞介导的防御功能的影响 [J]. 中药药理与临床 , 1998 , 14 ( 6 ): 18 - 20 .
张秀芬 , 王思梦 , 白建英 , 等 . 经典名方地黄饮子的古代文献考究 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 14 ): 59 - 64 .
高山 , 谢宁 , 刘钊 , 等 . 加味地黄饮子干预自然衰老大鼠免疫功能的实验研究 [J]. 环球中医药 , 2018 , 11 ( 4 ): 492 - 497 .
WYNN T A , CHAWLA A , POLLARD J W . Macrophage biology in development,homeostasis and disease [J]. Nature , 2013 , 496 ( 7446 ): 445 - 455 .
SHAPOURI-MOGHADDAM A , MOHAMMADIAN S , VAZINI H , et al . Macrophage plasticity,polarization,and function in health and disease [J]. J Cell Physiol , 2018 , 233 ( 9 ): 6425 - 6440 .
李仁述 . 生脉饮出处小考 [J]. 成都中医学院学报 , 1988 , 3 : 45 - 46 .
LI X , GAO J , YU Z , et al . Regulatory effect of anwulignan on the immune function through its antioxidation and anti-apoptosis in D -galactose-induced aging mice [J]. Clin Interv Aging , 2020 , 15 : 97 - 110 .
刘佳 , 张敬敬 , 李明阳 , 等 . 人参茎叶总皂苷对 D -半乳糖致衰老小鼠免疫功能的影响 [J]. 中国老年学杂志 , 2015 , 35 ( 18 ): 5087 - 5089 .
张景祖 . 人参鹿茸丸治疗少精症36例 [J]. 新中医 , 1994 ( S1 ): 52 .
LEE S K , WONG C K , POON P M , et al . In vitro immunomodulatory activities of a newly concocted traditional Chinese medicine formula:Ⅵ-28 [J]. Phytother Res , 2006 , 20 ( 10 ): 883 - 888 .
BANCHEREAU J , STEINMAN R M . Dendritic cells and the control of immunity [J]. Nature , 1998 , 392 ( 6673 ): 245 - 252 .
JING Y , SHAHEEN E , DRAKE R R , et al . Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells,whereas myeloid dendritic cells are relatively unaltered in human peripheral blood [J]. Hum Immunol , 2009 , 70 ( 10 ): 777 - 784 .
RAHMATPANAH F , AGRAWAL S , SCARFONE V M , et al . Transcriptional profiling of age-associated gene expression changes in human circulatory CD1c + myeloid dendritic cell subset [J]. J Gerontol A Biol Sci Med Sci , 2019 , 74 ( 1 ): 9 - 15 .
王东坡 , 李卫红 , 丁雷 , 等 . 玉屏风散释名、类方及其出处考证 [J]. 安徽中医药大学学报 , 2015 , 34 ( 3 ): 6 - 8 .
WANG X T , LIU H L , YU X , et al . Chinese medicine Yu-Ping-Feng-San attenuates allergic inflammation by regulating epithelial derived pro-allergic cytokines [J]. Chin J Nat Med , 2019 , 17 ( 7 ): 525 - 534 .
傅晓燕 , 雷珊珊 , 李雄英 . 黄芪配方颗粒对衰老大鼠认知功能的影响及机制初探 [J]. 中药材 , 2017 , 40 ( 5 ): 1184 - 1189 .
LI W , SUN Y N , YAN X T , et al . Flavonoids from Astragalus membranaceus and their inhibitory effects on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells [J]. Arch Pharm Res , 2014 , 37 ( 2 ): 186 - 192 .
CAMPOS C , PERA A , SANCHEZ-CORREA B , et al . Effect of age and CMV on NK cell subpopulations [J]. Exp Gerontol , 2014 , 54 : 130 - 137 .
CAMPOS C , PERA A , LOPEZ-FERNANDEZ I , et al . Proinflammatory status influences NK cells subsets in the elderly [J]. Immunol Lett , 2014 , 162 ( 1 Pt B ): 298 - 302 .
MARTÍN S , PÉREZ A , ALDECOA C . Sepsis and immunosenescence in the elderly patient:a review [J]. Front Med (Lausanne) , 2017 , 4 : 20 .
MÜLLER L , DI BENEDETTO S , PAWELEC G . The immune system and its dysregulation with aging [J]. Subcell Biochem , 2019 , 91 : 21 - 43 .
HAZELDINE J , LORD J M . The impact of ageing on natural killer cell function and potential consequences for health in older adults [J]. Ageing Res Rev , 2013 , 12 ( 4 ): 1069 - 1078 .
宋亚南 , 邓艳芳 , 屈乐 , 等 . 《丹溪心法》用药规律数据挖掘分析 [J]. 中医杂志 , 2015 , 56 ( 9 ): 796 - 800 .
ZHANG K , MA X , HE W , et al . Extracts of cistanche deserticola can antagonize immunosenescence and extend life span in senescence-accelerated mouse prone 8(SAM-P8)mice [J]. Evid Based Complement Alternat Med , 2014 , 2014 : 601383 .
张涛 , 柳朝阳 , 王建杰 , 等 . 肉苁蓉总苷对 D -半乳糖所致衰老模型小鼠免疫功能的影响 [J]. 中国老年学杂志 , 2004 , 24 ( 5 ): 441 - 442 .
GORONZY J J , WEYAND C M . Mechanisms underlying T cell ageing [J]. Nat Rev Immunol , 2019 , 19 ( 9 ): 573 - 583 .
ZHAO Y , SHAO Q , PENG G . Exhaustion and senescence:two crucial dysfunctional states of T cells in the tumor microenvironment [J]. Cell Mol Immunol , 2020 , 17 ( 1 ): 27 - 35 .
WEYAND C M , YANG Z , GORONZY J J . T-cell aging in rheumatoid arthritis [J]. Curr Opin Rheumatol , 2014 , 26 ( 1 ): 93 - 100 .
TURNER V M , MABBOTT N A . Structural and functional changes to lymph nodes in ageing mice [J]. Immunology , 2017 , 151 ( 2 ): 239 - 247 .
COHEN S , JANICKI-DEVERTS D , TURNER R B , et al . Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults [J]. JAMA , 2013 , 309 ( 7 ): 699 - 705 .
VENTURA M T , CASCIARO M , GANGEMI S , et al . Immunosenescence in aging:between immune cells depletion and cytokines up-regulation [J]. Clin Mol Allergy , 2017 , 15 : 21 .
ELYAHU Y , HEKSELMAN I , EIZENBERG-MAGAR I , et al . Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes [J]. Sci Adv , 2019 , 5 ( 8 ): eaaw8330 .
LI J , CHEN S , XIAO X , et al . IL-9 and Th9 cells in health and diseases-from tolerance to immunopathology [J]. Cytokine Growth Factor Rev , 2017 , 37 : 47 - 55 .
GASPARONI A , CIARDELLI L , AVANZINI A , et al . Age-related changes in intracellular TH1/TH2 cytokine production,immunoproliferative T lymphocyte response and natural killer cell activity in newborns,children and adults [J]. Biol Neonate , 2003 , 84 ( 4 ): 297 - 303 .
李慧平 , 年莉 . 六味地黄丸方剂的来源与方名释义 [J]. 天津中医药 , 2013 , 30 ( 3 ): 157 - 158 .
ZENG J , ZHANG X , WANG J , et al . Comparison of donepezil,memantine,melatonin,and liuwei dihuang decoction on behavioral and immune endocrine responses of aged senescence-accelerated mouse resistant 1 mice [J]. Front Pharmacol , 2020 , 11 : 350 .
WANG J , CHENG X , ZHANG X , et al . The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain [J]. Oncotarget , 2016 , 7 ( 19 ): 26949 - 26965 .
SALMINEN A , KAARNIRANTA K , KAUPPINEN A . Immunosenes cence:the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency [J]. Cell Mol Life Sci , 2019 , 76 ( 10 ): 1901 - 1918 .
BUFFA S , BULATI M , PELLICANÒ M , et al . B cell immunosenescence:different features of naïve and memory B cells in elderly [J]. Biogerontology , 2011 , 12 ( 5 ): 473 - 483 .
BULATI M , BUFFA S , CANDORE G , et al . B cells and immunosenescence:a focus on IgG + IgD - CD27 - (DN) B cells in aged humans [J]. Ageing Res Rev , 2011 , 10 ( 2 ): 274284 .
廖洪峰 , 王桂敏 , 李明慧 , 等 . 首乌延寿丹对去势后大鼠骨质疏松的防治作用 [J]. 中国中医基础医学杂志 , 2012 , 18 ( 1 ): 61 - 62 .
石桂英 , 白琳 . 长期食用何首乌对小鼠造血系统的影响 [J]. 中国比较医学杂志 , 2016 , 26 ( 12 ): 10 - 13 .
柏原直樹 . 加齢と腎臓 [J]. 日本内科学会雑誌 , 2018 ,107(Suppl 号):125b.
成海燕 , 于建春 , 李国民 , 等 . 衰老-血瘀相关研究概况 [J]. 辽宁中医杂志 , 2010 , 37 ( 9 ): 1660 - 1663 .
TU Y , LIU B , WAN Y . Dahuang Zhechong Pill attenuates D -galactose induced renal aging by targeting autophagy via regulation of T-cells in kidney and spleen [C]// Washington,DC (USA) : The American Society of Nephrology,ASN "Kidney Week® 2019 : 52th Annual Meeting" ,2019.
0
Views
30
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621