端粒与心血管衰老及补肾活血中药干预的相关性
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摘要
随着世界老龄化的进展,目前衰老及衰老相关的心血管疾病已经成为医疗的重要关注方向。衰老是一个普遍和多因素的过程,其特点是生理功能逐渐下降,细胞功能障碍,引起多种疾病。目前端粒缩短成为血管老化的一个标志。端粒长度的缩短因暴露于吸烟、肥胖等因素而加速。端粒缩短和功能障碍在老年性相关心血管疾病的发病机制中起着至关重要的作用。心血管危险因素,如吸烟、高血压、糖尿病、肥胖和压力等,都被认为会增加氧化应激或炎症,加速端粒的缩短,相反健康的生活方式可以保护和维持端粒长度。既往研究也表明端粒缩短与动脉粥样硬化性心血管疾病密切相关。这可能是心血管疾病危险分层的一个有效的生物标志物。传统医学认为,人体衰老和肾精亏虚相伴而至。而心肾之间相互关联,相互制约,而成水火既济。"心主身之血脉",肾虚所致的心功能受损和心的自身衰老都会引起相关的心血管疾病。研究发现活血化瘀中药,及多个具有补肾功效的中药或方剂很有可能通过改变端粒长度和端粒酶活性,影响改善心血管相关的疾病。在当今老龄化社会的进程中,在广阔的中医药宝库中进一步挖掘,于多种活血化瘀中药及补肾中药中进一步探索,从端粒角度研究中医药干预心血管衰老的病理机制对心血管疾病的防治具有重要意义。
With the advance of aging in the world,aging and its relevant cardiovascular diseases have become an important concern for medical care.Aging is a universal and multifactorial process characterized by a gradual decline in physiological functions,cell dysfunction and a variety of diseases.Telomere shortening is currently a hallmark of vascular aging.The shortening of telomere length is accelerated by exposure to smoking,obesity and other factors.Telomere shortening and dysfunction play crucial roles in the pathogenesis of senilerelated cardiovascular diseases.Cardiovascular risk factors,such as smoking,high blood pressure,diabetes,obesity and stress are considered to increase oxidative stress or inflammation,accelerate the shortening of telomeres,and protect the healthy telomere length.Previous studies have also shown that telomere shortening is closely related to atherosclerotic cardiovascular disease.This may be an effective biomarker for the risk stratification of cardiovascular disease.According to the theory of traditional Chinese medicine(TCM),human aging and kidney deficiency are accompanied.The heart and kidney are interrelated and mutually constrained for coordinating water and fire.Impaired heart function due to kidney deficiency and self-aging can cause relevant cardiovascular diseases.The study found that TCM or prescriptions for activating blood circulation to remove blood stasis and many kidney-reinforcing TCM or prescriptions are likely to affect cardiovascular diseases by altering telomere length and telomerase activity.In today ' s aging society,TCM for promoting blood circulation,removing blood stasis and tonifying kidney from the perspective of telomere is of great significance for the pathological mechanism of cardiovascular diseases.
With the advance of aging in the world,aging and its relevant cardiovascular diseases have become an important concern for medical care.Aging is a universal and multifactorial process characterized by a gradual decline in physiological functions,cell dysfunction and a variety of diseases.Telomere shortening is currently a hallmark of vascular aging.The shortening of telomere length is accelerated by exposure to smoking,obesity and other factors.Telomere shortening and dysfunction play crucial roles in the pathogenesis of senilerelated cardiovascular diseases.Cardiovascular risk factors,such as smoking,high blood pressure,diabetes,obesity and stress are considered to increase oxidative stress or inflammation,accelerate the shortening of telomeres,and protect the healthy telomere length.Previous studies have also shown that telomere shortening is closely related to atherosclerotic cardiovascular disease.This may be an effective biomarker for the risk stratification of cardiovascular disease.According to the theory of traditional Chinese medicine(TCM),human aging and kidney deficiency are accompanied.The heart and kidney are interrelated and mutually constrained for coordinating water and fire.Impaired heart function due to kidney deficiency and self-aging can cause relevant cardiovascular diseases.The study found that TCM or prescriptions for activating blood circulation to remove blood stasis and many kidney-reinforcing TCM or prescriptions are likely to affect cardiovascular diseases by altering telomere length and telomerase activity.In today ' s aging society,TCM for promoting blood circulation,removing blood stasis and tonifying kidney from the perspective of telomere is of great significance for the pathological mechanism of cardiovascular diseases.
引文
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[4]Campisi J.Aging,cellular senescence,and cancer[J].Annu Rev Physiol,2013,75(1):685-705.
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[8]黄晓燕,马媛萍,李桂贤,等.四君子汤含药血清调控h TERT,TRF1,Tankyrase表达及对UCAC的影响[J].中国实验方剂学杂志,2018,24(8):128-133.
[9]黄毕,杨艳敏.端粒长度与心血管疾病关系的研究进展[J].中国循环杂志,2013,28(7):555-557.
[10]吕涛,郭文怡.端粒长度与心血管疾病危险因素关系的研究进展[J].心脏杂志,2018,30(5):85-89,103.
[11]CHEN Y,YANG Y,van Overbeek M,et al.A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins[J].Science,2008,319(5866):1092-1096.
[12]Sahin E,Colla S,Liesa M,et al.Telomere dysfunction induces metabolic and mitochondrial compromise[J].Nature,2011,470(7334):359-365.
[13]Harrington L,Pucci F.In medio stat virtus:unanticipated consequences of telomere dysequilibrium[J].Philos Trans R Soc Lond B Biol Sci,2018,373(1741):20160444.
[14]王镜辉,唐东昕,黄慧,等.葛花解酲方对肝癌细胞原位移植瘤小鼠端粒酶蛋白表达水平的影响[J].中国实验方剂学杂志,2015,21(24):73-78.
[15]Invernizzi P,Bernuzzi F,Lleo A,et al.Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis[J].Dig Liver Dis,2014,46(4):363-368.
[16]Fulop T,Larbi A,Dupuis G,et al.Immunosenescence and inflamm-aging as two sides of the same coin:friends or foes?[J].Front Immunol,2018,8:1960.
[17]Jacobs E G,Epel E S,LIN J,et al.Relationship between leukocyte telomere length,telomerase activity,and hippocampal volume in early aging[J].JAMANeurol,2014,71(7):921-923.
[18]Gazzaniga F S,Blackburn E H.An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity[J].Blood,2014,124(25):3675-3684.
[19]Ozturk M B,LI Y,Tergaonkar V,et al.Current insights to regulation and role of telomerase in human diseases[J].Antioxidants,2017,6(1):E17.
[20]Ellehoj H,Bendix L,Osler M.Leucocyte Telomere length and risk of cardiovascular disease in a cohort of1,397 danish men and women[J].Cardiology,2016,133(3):173-177.
[21]Barrett E L,Burke T A,Hammers M,et al.Telomere length and dynamics predict mortality in a wild longitudinal study[J].Mol Ecol,2013,22(1):249-259.
[22]De Punder K,Heim C,Przesdzing I,et al.Characterization of in vitro leukocyte maximal telomerase activity capacity(m TAC)in humans:association with chronic stress exposure and stress-reactivity[J].Brain Behav Immun,2017,66:e17.
[23]Mathur M B,Epel E,Kind S,et al.Perceived stress and telomere length:a systematic review,Metaanalysis,and methodologic considerations for advancing the field[J].Brain Behav Immun,2016,54:158-169.
[24]Miller G E,Murphy M L,Cashman R,et al.Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers[J].Brain Behav Immun,2014,41(10):191-199.
[25]Oliveira B S,Zunzunegui M V,Quinlan J,et al.Systematic review of the association between chronic social stress and telomere length:a life course perspective[J].Ageing Res Rev,2016,26(5):37-52.
[26]LIU Y,Bloom S I,Donato A J.The Role of senescence,telomere dysfunction and shelterin in vascular aging[J].Microcirculation,2019,26(2):e12487.
[27]胡明彦.心肾核心说理论构建与应用研究[J].中华中医药杂志,2009,24(10):1381-1383.
[28]张怀亮,刘群霞.浅议命门之火、君火、相火及其关系[J].中华中医药杂志,2015,30(4):1131-1133.
[29]刘欣,郭春雨,王景尚,等.肾精、端粒酶与血管老化[J].医学研究杂志,2014,43(12):148-151.
[30]李淑玲,刘凯,赵信科,等.当归红芪多糖对急性心肌缺血大鼠的保护作用[J].中国实验方剂学杂志,2016,22(17):92-96.
[31]张先平.当归多糖调控造血干细胞衰老的机制研究[D].重庆:重庆医科大学,2013.
[32]张宝霞,张金生,许二平,等.补肾化瘀生新法协同静脉注射骨髓间充质干细胞对延缓大鼠衰老作用[J].中国实验方剂学杂志,2018,24(24):116-121.
[33]熊平,蒋灵芝,黄兆胜.补肾活血化痰中药复方对D-半乳糖诱发衰老模型大鼠中枢神经递质及β-淀粉样蛋白的影响[J].中国实验方剂学杂志,2007,13(2):42-45.
[34]彭程飞,李佳,田孝祥,等.人参皂苷Rg1抑制大鼠急性心肌梗死后心肌纤维化[J].现代生物医学进展,2017,17(16):3005-3007,3128.
[35]文飞,杨萍,赖婷婷,等.人参皂苷Rg1预处理对大鼠离体心缺血/再灌注损伤的保护作用[J].解剖学杂志,2016,39(6):673-677.
[36]赵朝晖,陈晓春,朱元贵,等.人参皂苷Rg1延缓细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国药理学通报,2005,21(1):61-66.
[37]周玥,姜蓉,杨斌,等.人参皂苷Rg1延缓造血干细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国中药杂志,2011,36(22):3172-3175.
[38]张洪泉,李媛,宋媛媛.肉苁蓉多糖对衰老小鼠免疫细胞和端粒酶活性的影响[J].中国药学杂志,2011,46(14):1081-1083.
[39]阮景明,叶章正,黄华玮,等.虫草提取物对高糖诱导的脐静脉内皮细胞损伤模型的保护作用[J].中华老年心脑血管病杂志,2013,15(10):1067-1071.
[40]LIU A,WU J,LI A,et al.The inhibitory mechanism of cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells[J].Int JChron Obstruct Pulmon Dis,2016,11(issue 1):1721-1731.
[41]蒋万志,张洪泉.枸杞多肽对D-半乳糖诱导小鼠的抗衰老作用及其可能机制[J].国际药学研究杂志,2010,37(1):47-50.
[42]楼丹飞,李越华,闫国良.样补肾活血方对动脉粥样硬化新西兰兔miRNA217的影响[J].四川中医,2016,34(10):31-33.
[43]陈川,迟惠英,郁志华,等.首参颗粒对动脉粥样硬化大鼠血管细胞与外周血白细胞端粒和端粒酶的影响[J].中西医结合学报,2012,10(6):667-673.
[44]楼丹飞,申定珠,陈川,等.首参颗粒对颈动脉硬化患者端粒及端粒酶的影响[J].四川中医,2013,31(11):40-43.
[45]张秀荣,薛一涛.真武汤合保元汤对2型心肾综合征阳气亏虚证兼血瘀证心肾功能的影响[J].中国实验方剂学杂志,2018,24(9):202-207.
[2]López-Otín C,Blasco M A,Partridge L,et al.The hallmarks of aging[J].Cell,2013,153(6):1194-1217.
[3]Hayflick L.The limited in vitro lifetime of human diploid cell strains[J].Exp Cell Res,1965,37(3):614-636.
[4]Campisi J.Aging,cellular senescence,and cancer[J].Annu Rev Physiol,2013,75(1):685-705.
[5]Ornish D,LIN J,CHAN J M,et al.Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer:5-year follow-up of a descriptive pilot study[J].Lancet Oncol,2013,14(11):1112-1120.
[6]Haycock P C,Heydon E E,Kaptoge S,et al.Leucocyte telomere length and risk of cardiovascular disease:systematic review and Meta-analysis[J].BMJ,2014,349:g4227.
[7]D'Mello M J,Ross S A,Briel M,et al.Association between shortened leukocyte telomere length and cardiometabolic outcomes:systematic review and Metaanalysis[J].Circ Cardiovasc Genet,2015,8(1):82-90.
[8]黄晓燕,马媛萍,李桂贤,等.四君子汤含药血清调控h TERT,TRF1,Tankyrase表达及对UCAC的影响[J].中国实验方剂学杂志,2018,24(8):128-133.
[9]黄毕,杨艳敏.端粒长度与心血管疾病关系的研究进展[J].中国循环杂志,2013,28(7):555-557.
[10]吕涛,郭文怡.端粒长度与心血管疾病危险因素关系的研究进展[J].心脏杂志,2018,30(5):85-89,103.
[11]CHEN Y,YANG Y,van Overbeek M,et al.A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins[J].Science,2008,319(5866):1092-1096.
[12]Sahin E,Colla S,Liesa M,et al.Telomere dysfunction induces metabolic and mitochondrial compromise[J].Nature,2011,470(7334):359-365.
[13]Harrington L,Pucci F.In medio stat virtus:unanticipated consequences of telomere dysequilibrium[J].Philos Trans R Soc Lond B Biol Sci,2018,373(1741):20160444.
[14]王镜辉,唐东昕,黄慧,等.葛花解酲方对肝癌细胞原位移植瘤小鼠端粒酶蛋白表达水平的影响[J].中国实验方剂学杂志,2015,21(24):73-78.
[15]Invernizzi P,Bernuzzi F,Lleo A,et al.Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis[J].Dig Liver Dis,2014,46(4):363-368.
[16]Fulop T,Larbi A,Dupuis G,et al.Immunosenescence and inflamm-aging as two sides of the same coin:friends or foes?[J].Front Immunol,2018,8:1960.
[17]Jacobs E G,Epel E S,LIN J,et al.Relationship between leukocyte telomere length,telomerase activity,and hippocampal volume in early aging[J].JAMANeurol,2014,71(7):921-923.
[18]Gazzaniga F S,Blackburn E H.An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity[J].Blood,2014,124(25):3675-3684.
[19]Ozturk M B,LI Y,Tergaonkar V,et al.Current insights to regulation and role of telomerase in human diseases[J].Antioxidants,2017,6(1):E17.
[20]Ellehoj H,Bendix L,Osler M.Leucocyte Telomere length and risk of cardiovascular disease in a cohort of1,397 danish men and women[J].Cardiology,2016,133(3):173-177.
[21]Barrett E L,Burke T A,Hammers M,et al.Telomere length and dynamics predict mortality in a wild longitudinal study[J].Mol Ecol,2013,22(1):249-259.
[22]De Punder K,Heim C,Przesdzing I,et al.Characterization of in vitro leukocyte maximal telomerase activity capacity(m TAC)in humans:association with chronic stress exposure and stress-reactivity[J].Brain Behav Immun,2017,66:e17.
[23]Mathur M B,Epel E,Kind S,et al.Perceived stress and telomere length:a systematic review,Metaanalysis,and methodologic considerations for advancing the field[J].Brain Behav Immun,2016,54:158-169.
[24]Miller G E,Murphy M L,Cashman R,et al.Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers[J].Brain Behav Immun,2014,41(10):191-199.
[25]Oliveira B S,Zunzunegui M V,Quinlan J,et al.Systematic review of the association between chronic social stress and telomere length:a life course perspective[J].Ageing Res Rev,2016,26(5):37-52.
[26]LIU Y,Bloom S I,Donato A J.The Role of senescence,telomere dysfunction and shelterin in vascular aging[J].Microcirculation,2019,26(2):e12487.
[27]胡明彦.心肾核心说理论构建与应用研究[J].中华中医药杂志,2009,24(10):1381-1383.
[28]张怀亮,刘群霞.浅议命门之火、君火、相火及其关系[J].中华中医药杂志,2015,30(4):1131-1133.
[29]刘欣,郭春雨,王景尚,等.肾精、端粒酶与血管老化[J].医学研究杂志,2014,43(12):148-151.
[30]李淑玲,刘凯,赵信科,等.当归红芪多糖对急性心肌缺血大鼠的保护作用[J].中国实验方剂学杂志,2016,22(17):92-96.
[31]张先平.当归多糖调控造血干细胞衰老的机制研究[D].重庆:重庆医科大学,2013.
[32]张宝霞,张金生,许二平,等.补肾化瘀生新法协同静脉注射骨髓间充质干细胞对延缓大鼠衰老作用[J].中国实验方剂学杂志,2018,24(24):116-121.
[33]熊平,蒋灵芝,黄兆胜.补肾活血化痰中药复方对D-半乳糖诱发衰老模型大鼠中枢神经递质及β-淀粉样蛋白的影响[J].中国实验方剂学杂志,2007,13(2):42-45.
[34]彭程飞,李佳,田孝祥,等.人参皂苷Rg1抑制大鼠急性心肌梗死后心肌纤维化[J].现代生物医学进展,2017,17(16):3005-3007,3128.
[35]文飞,杨萍,赖婷婷,等.人参皂苷Rg1预处理对大鼠离体心缺血/再灌注损伤的保护作用[J].解剖学杂志,2016,39(6):673-677.
[36]赵朝晖,陈晓春,朱元贵,等.人参皂苷Rg1延缓细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国药理学通报,2005,21(1):61-66.
[37]周玥,姜蓉,杨斌,等.人参皂苷Rg1延缓造血干细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国中药杂志,2011,36(22):3172-3175.
[38]张洪泉,李媛,宋媛媛.肉苁蓉多糖对衰老小鼠免疫细胞和端粒酶活性的影响[J].中国药学杂志,2011,46(14):1081-1083.
[39]阮景明,叶章正,黄华玮,等.虫草提取物对高糖诱导的脐静脉内皮细胞损伤模型的保护作用[J].中华老年心脑血管病杂志,2013,15(10):1067-1071.
[40]LIU A,WU J,LI A,et al.The inhibitory mechanism of cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells[J].Int JChron Obstruct Pulmon Dis,2016,11(issue 1):1721-1731.
[41]蒋万志,张洪泉.枸杞多肽对D-半乳糖诱导小鼠的抗衰老作用及其可能机制[J].国际药学研究杂志,2010,37(1):47-50.
[42]楼丹飞,李越华,闫国良.样补肾活血方对动脉粥样硬化新西兰兔miRNA217的影响[J].四川中医,2016,34(10):31-33.
[43]陈川,迟惠英,郁志华,等.首参颗粒对动脉粥样硬化大鼠血管细胞与外周血白细胞端粒和端粒酶的影响[J].中西医结合学报,2012,10(6):667-673.
[44]楼丹飞,申定珠,陈川,等.首参颗粒对颈动脉硬化患者端粒及端粒酶的影响[J].四川中医,2013,31(11):40-43.
[45]张秀荣,薛一涛.真武汤合保元汤对2型心肾综合征阳气亏虚证兼血瘀证心肾功能的影响[J].中国实验方剂学杂志,2018,24(9):202-207.