针灸调节内质网应激的研究进展
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摘要
内质网(ER)是蛋白质修饰、折叠和Ca2+贮存的场所,ER内稳态失衡时,即发生内质网应激(ERS)。ERS及其诱导的凋亡与许多疾病的发生发展密切相关。针灸能够影响细胞ERS以及细胞凋亡因子的表达而调节ERS。本文综述了近5年针灸调节神经系统疾病、糖尿病、心血管疾病、非酒精性脂肪肝等相关疾病细胞ERS的研究进展,为阐释针灸防治相关疾病的可能机制提供参考。
Endoplasmic reticulum stress(ERS)is one of the major defense networks in mammals,but continuous ERS will lead to cell apoptosis,inducing initiation and progression of many human diseases.Biochemical,physiological and pathological stimuli induced ERS may help the cells adapt to and survive stress conditions by activating unfolded protein response(UPR),ERoverload response and sterol modulation cascade reaction.Abundant outcomes of clinical and experimental studies in recent5 years showed that acupuncture and moxibustion therapies are effective in improving some symptoms of nervous system diseases as stroke,Parkinson's disease,convulsion,cardiovascular diseases,diabetes mellitus,non-alcoholic fatty liver disease,spinal cord injury,muscular injury,etc.,which is closely associated with their functions in relieving excessive ERS and cell apoptosis via modulating UPR pathway.Some important molecules or signaling pathways such as glucose-regulated protein 78(GRP78),Caspase-12,ER transmembrane kinase inositol-requiring and ER-to-nucleus signaling protein(IRE1 P),phosphorylated extracellular signal-regulated kinase(p-ERK)/eukaryotic translation initiation factor 2α(eIF2α),activating transcription factor 4(ATF4),CCAAT/enhancer-binding protein homologous protein(CHOP),etc.have been demonstrated to be involved in the effects of acupuncture-moxibustion interventions.But,the mechanism of acupuncture-moxibustion underlying improvement of ERS remains far more unclear.Future studies targeting the combination of molecules and holistic function,verification of changes of the involved protein molecules and multiple signaling pathways,balancing regulation between the cell survival and apoptosis,etc.by adopting syndrome-differentiation-based acupoints are definitely needed.
Endoplasmic reticulum stress(ERS)is one of the major defense networks in mammals,but continuous ERS will lead to cell apoptosis,inducing initiation and progression of many human diseases.Biochemical,physiological and pathological stimuli induced ERS may help the cells adapt to and survive stress conditions by activating unfolded protein response(UPR),ERoverload response and sterol modulation cascade reaction.Abundant outcomes of clinical and experimental studies in recent5 years showed that acupuncture and moxibustion therapies are effective in improving some symptoms of nervous system diseases as stroke,Parkinson's disease,convulsion,cardiovascular diseases,diabetes mellitus,non-alcoholic fatty liver disease,spinal cord injury,muscular injury,etc.,which is closely associated with their functions in relieving excessive ERS and cell apoptosis via modulating UPR pathway.Some important molecules or signaling pathways such as glucose-regulated protein 78(GRP78),Caspase-12,ER transmembrane kinase inositol-requiring and ER-to-nucleus signaling protein(IRE1 P),phosphorylated extracellular signal-regulated kinase(p-ERK)/eukaryotic translation initiation factor 2α(eIF2α),activating transcription factor 4(ATF4),CCAAT/enhancer-binding protein homologous protein(CHOP),etc.have been demonstrated to be involved in the effects of acupuncture-moxibustion interventions.But,the mechanism of acupuncture-moxibustion underlying improvement of ERS remains far more unclear.Future studies targeting the combination of molecules and holistic function,verification of changes of the involved protein molecules and multiple signaling pathways,balancing regulation between the cell survival and apoptosis,etc.by adopting syndrome-differentiation-based acupoints are definitely needed.
引文
[1]朱海英,肖淑萍,孙红玉.内质网应激在大鼠脑缺血再灌注损伤中的作用研究[J].中华神经医学杂志,2013,12(4):359-363.
[2]van DER KALLEN C J,van GREEVENBROEK M M,STE-HOUWER C D,et al.Endoplasmic reticulum stress-induced apoptosis in the development of diabetes:is there a role for adipose tissue and liver[J].Apoptosis,2009,14(12):1424-1434.
[3]TOTH A,NICKSON P,MANDL A,et al.Endoplasmic reticulum stress as a novel therapeutic target in heart disease[J].Cardiovasc Hematol Disord Drug Targets,2007,7(3):205-218.
[4]HUANG N,YU Y,QIAO J.Dual role for the unfolded protein response in the ovary:adaption and apoptosis[J].Protein Cell,2017,8(1):14-24.
[5]WALTER P,RON D.The unfolded protein response:from stress pathway to homeostatic regulation[J].Science,2011,334(6059):1081-1086.
[6]WAHYUINDRADUWI F,LEE S Y,LEE K O.The unfolded protein response in plants:a fundamental adaptive cellular response to internal and external stresses[J].J Proteomics,2013,93:356-368
[7]CHEN X,LI M,CHEN D,et al.Autophagy induced by calcium phosphate precipitates involves endoplasmic reticulum membranes in autophagosome biogenesis[J].PLoS One,2012,7(12):e52347.
[8]OGATA M,HINO S,SAITO A,et al.Autophagy is activated for cell survival after endoplasmic reticulum stress[J].Mol Cell Biol,2006,26(24):9220-9231.
[9]KOUROKU Y,FUJITA E,TANIDA I,et al.ER stress(PERK/e IF2al-pha phosphorylation)mediates the polyglutamine-induced LC3conversion,an essential step for autophagy formation[J].Cell Death Differ,2007,14(2):230-239.
[10]侯亚菊.针灸对缺血性脑血管病颈动脉粥样硬化患者的临床疗效分析[J].当代医学,2013,19(23):151-152.
[11]吕少君.针灸治疗急性缺血性脑血管病的临床分析[J].中国医药指南,2013,7(11):673-674.
[12]孙会芳,姜雪,刘晓静,等.针刺对缺血性脑血管病脑血流量的影响[J].吉林中医药,2013,33(5):506-508.
[13]沈菁,雷晓明,宋洋,等.电针内关、百会穴对脑缺血/再灌注大鼠GRP78和Caspase-12基因表达的影响[J].湖南中医药大学,2016,36(2):54-57.
[14]郁洁,宋洋,谭杏,等.针刺对实验性脑缺血大鼠内质网未折叠蛋白反应通路eIF2α基因表达的影响[J].中医药导报,2014,20(10):11-14.
[15]邹伟,牛明明,于学平,等.“百会”透“曲鬓”针刺法对脑出血大鼠脑组织中PERK蛋白表达影响的实验研究[J].中医药信息,2017,34(2):75-79.
[16]王述菊,王中明,马骏,等.电针对帕金森病模型大鼠黑质内质网应激相关基因表达的影响[J].时珍国医国药,2017,28(6):1497-1500.
[17]马骏,王中明,王述菊,等.电针对帕金森病模型大鼠黑质内Bip、CHOP蛋白表达的影响[J].上海针灸杂志,2018,37(1):86-91.
[18]BENGZON J,MOHAPEL P,EKDAHL C T,et al.Neuronal apoptosis after brief and prolonged seizures[J].Prog Brain Res,2002,135:111-119
[19]AMPUERO E,DAGNINO-SUBIABRE A,SANDOVAL R,et al.Status epilepticus induces region-specific changes indendritic spines,dendritic length and TrkB protein content of rat brain cortex[J].Brain Res,2007,1150(2):225-238.
[20]杨帆,马允,昂文平,等.针刺对戊四唑诱发惊厥大鼠海马葡萄糖调节蛋白78和C/EBP同源蛋白表达的影响[J].针刺研究,2014,39(4):267-271.
[21]张慧,杨帆,吴旭,等.针刺血清调控内质网应激反应对无镁诱导培养大鼠海马神经元惊厥性损伤的保护作用[J].针刺研究,2017,42(2):95-101.
[22]李瑞午,张金铃,郭莹,等.针灸血清对大脑皮层细胞内钙离子的影响初探-针灸体液机理的研究[J].中国针灸,2005,25(5):351-354.
[23]张金铃,李瑞午,郭莹,等.针刺血清对培养海马神经元内质网活性的上调作用[J].辽宁中医药大学学报,2011,13(9):38-39.
[24]张道芹,张阳,张荣军,等.针刺对海洛因复吸大鼠脑组织GRP78和CRT表达的影响[J].安徽中医药大学学报,2015,34(2):45-48.
[25]高永龙,张阳,宋小鸽,等.针刺对海洛因成瘾大鼠脑损伤神经保护作用[J].中医药临床杂志,2017,29(1):82-87.
[26]MURRY C E,JENNINGS R B,REIMER K A.Preconditioning with ischemic:a delay of lethal cell injury ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[27]陈怀龙,齐慧,刘孝洁,等.电针预处理对全脑缺血再灌注损伤大鼠海马葡萄糖调节蛋白78和生长停滞及DNA损伤基因153表达的影响[J].针刺研究,2014,39(6):431-436.
[28]陈怀龙,齐慧,刘孝洁,等.电针预处理对大鼠全脑缺血再灌注时内质网应激的影响[J].中华麻醉学杂志,2014,34(3):331-333.
[29]唐祎周,孙忠人,张翀,等.夹脊电针对脊髓损伤大鼠内质网应激相关因子IRE1影响的实验研究[J].针灸临床杂志,2013,29(8):55-58.
[30]尹洪娜,孙忠人,李全,等.电针夹脊穴对脊髓损伤大鼠内质网应激相关因子Caspase-12影响的实验研究[J].中医药学报,2016,44(3):33-36.
[31]尹洪娜,孙忠人,李全,等.电针夹脊穴对脊髓损伤大鼠内质网应激相关因子CHOP影响的实验研究[J].中医药信息,2016,33(4):35-38.
[32]翟昌林,唐关敏,胡惠林,等.针灸预处理对大鼠心肌缺血再灌注后内质网应激的影响[J].中华危重症医学杂志(电子版),2014,7(3):172-175.
[33]RIEUSSET J.Mitochondria and endoplasmic reticulum:mitochondria-endoplasmic reticulum interplay in type 2diabetes pathophysiology[J].Int J Biochem Cell Biol,2011,43(9):1257-1262.
[34]袁爱红,查必祥,吴吉萍,等.针刺对糖尿病大鼠胰腺内质网应激PERK-CHOP途径与Bax/Bcl-2基因表达的影响[J].中华中医药杂志,2017,32(3):1291-1294.
[35]邵俊,查必祥,袁爱红,等.电针对糖尿病大鼠胰腺组织CHOP、Bax、Bcl-2蛋白表达及胰腺超微结构的影响[J].安徽中医药大学学报,2015,34(6):501-504.
[36]张毅,唐成林,田源,等.电针对非酒精性脂肪性肝病大鼠蛋白质二硫化物异构酶A3的影响[J].四川大学学报(医学版),2016,47(2):208-213.
[37]张毅,唐成林,田源,等.电针联合饮食调控对非乙醇性脂肪肝病大鼠肝脏内质网应激的影响[J].中国针灸,2016,36(9):951-956.
[38]余敏,李钢,唐成林,等.电针“丰隆”穴对非酒精性脂肪肝大鼠肝组织固醇调节元件结合蛋白-1c的影响[J].针刺研究,2017,42(4):308-314.
[39]丁海丽,孙竹昕,王海牛,等.大负荷运动及针刺干预对大鼠骨骼肌内质网应激钙信号的影响[J].北京体育大学学报,2017,40(11):49-55.
[2]van DER KALLEN C J,van GREEVENBROEK M M,STE-HOUWER C D,et al.Endoplasmic reticulum stress-induced apoptosis in the development of diabetes:is there a role for adipose tissue and liver[J].Apoptosis,2009,14(12):1424-1434.
[3]TOTH A,NICKSON P,MANDL A,et al.Endoplasmic reticulum stress as a novel therapeutic target in heart disease[J].Cardiovasc Hematol Disord Drug Targets,2007,7(3):205-218.
[4]HUANG N,YU Y,QIAO J.Dual role for the unfolded protein response in the ovary:adaption and apoptosis[J].Protein Cell,2017,8(1):14-24.
[5]WALTER P,RON D.The unfolded protein response:from stress pathway to homeostatic regulation[J].Science,2011,334(6059):1081-1086.
[6]WAHYUINDRADUWI F,LEE S Y,LEE K O.The unfolded protein response in plants:a fundamental adaptive cellular response to internal and external stresses[J].J Proteomics,2013,93:356-368
[7]CHEN X,LI M,CHEN D,et al.Autophagy induced by calcium phosphate precipitates involves endoplasmic reticulum membranes in autophagosome biogenesis[J].PLoS One,2012,7(12):e52347.
[8]OGATA M,HINO S,SAITO A,et al.Autophagy is activated for cell survival after endoplasmic reticulum stress[J].Mol Cell Biol,2006,26(24):9220-9231.
[9]KOUROKU Y,FUJITA E,TANIDA I,et al.ER stress(PERK/e IF2al-pha phosphorylation)mediates the polyglutamine-induced LC3conversion,an essential step for autophagy formation[J].Cell Death Differ,2007,14(2):230-239.
[10]侯亚菊.针灸对缺血性脑血管病颈动脉粥样硬化患者的临床疗效分析[J].当代医学,2013,19(23):151-152.
[11]吕少君.针灸治疗急性缺血性脑血管病的临床分析[J].中国医药指南,2013,7(11):673-674.
[12]孙会芳,姜雪,刘晓静,等.针刺对缺血性脑血管病脑血流量的影响[J].吉林中医药,2013,33(5):506-508.
[13]沈菁,雷晓明,宋洋,等.电针内关、百会穴对脑缺血/再灌注大鼠GRP78和Caspase-12基因表达的影响[J].湖南中医药大学,2016,36(2):54-57.
[14]郁洁,宋洋,谭杏,等.针刺对实验性脑缺血大鼠内质网未折叠蛋白反应通路eIF2α基因表达的影响[J].中医药导报,2014,20(10):11-14.
[15]邹伟,牛明明,于学平,等.“百会”透“曲鬓”针刺法对脑出血大鼠脑组织中PERK蛋白表达影响的实验研究[J].中医药信息,2017,34(2):75-79.
[16]王述菊,王中明,马骏,等.电针对帕金森病模型大鼠黑质内质网应激相关基因表达的影响[J].时珍国医国药,2017,28(6):1497-1500.
[17]马骏,王中明,王述菊,等.电针对帕金森病模型大鼠黑质内Bip、CHOP蛋白表达的影响[J].上海针灸杂志,2018,37(1):86-91.
[18]BENGZON J,MOHAPEL P,EKDAHL C T,et al.Neuronal apoptosis after brief and prolonged seizures[J].Prog Brain Res,2002,135:111-119
[19]AMPUERO E,DAGNINO-SUBIABRE A,SANDOVAL R,et al.Status epilepticus induces region-specific changes indendritic spines,dendritic length and TrkB protein content of rat brain cortex[J].Brain Res,2007,1150(2):225-238.
[20]杨帆,马允,昂文平,等.针刺对戊四唑诱发惊厥大鼠海马葡萄糖调节蛋白78和C/EBP同源蛋白表达的影响[J].针刺研究,2014,39(4):267-271.
[21]张慧,杨帆,吴旭,等.针刺血清调控内质网应激反应对无镁诱导培养大鼠海马神经元惊厥性损伤的保护作用[J].针刺研究,2017,42(2):95-101.
[22]李瑞午,张金铃,郭莹,等.针灸血清对大脑皮层细胞内钙离子的影响初探-针灸体液机理的研究[J].中国针灸,2005,25(5):351-354.
[23]张金铃,李瑞午,郭莹,等.针刺血清对培养海马神经元内质网活性的上调作用[J].辽宁中医药大学学报,2011,13(9):38-39.
[24]张道芹,张阳,张荣军,等.针刺对海洛因复吸大鼠脑组织GRP78和CRT表达的影响[J].安徽中医药大学学报,2015,34(2):45-48.
[25]高永龙,张阳,宋小鸽,等.针刺对海洛因成瘾大鼠脑损伤神经保护作用[J].中医药临床杂志,2017,29(1):82-87.
[26]MURRY C E,JENNINGS R B,REIMER K A.Preconditioning with ischemic:a delay of lethal cell injury ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[27]陈怀龙,齐慧,刘孝洁,等.电针预处理对全脑缺血再灌注损伤大鼠海马葡萄糖调节蛋白78和生长停滞及DNA损伤基因153表达的影响[J].针刺研究,2014,39(6):431-436.
[28]陈怀龙,齐慧,刘孝洁,等.电针预处理对大鼠全脑缺血再灌注时内质网应激的影响[J].中华麻醉学杂志,2014,34(3):331-333.
[29]唐祎周,孙忠人,张翀,等.夹脊电针对脊髓损伤大鼠内质网应激相关因子IRE1影响的实验研究[J].针灸临床杂志,2013,29(8):55-58.
[30]尹洪娜,孙忠人,李全,等.电针夹脊穴对脊髓损伤大鼠内质网应激相关因子Caspase-12影响的实验研究[J].中医药学报,2016,44(3):33-36.
[31]尹洪娜,孙忠人,李全,等.电针夹脊穴对脊髓损伤大鼠内质网应激相关因子CHOP影响的实验研究[J].中医药信息,2016,33(4):35-38.
[32]翟昌林,唐关敏,胡惠林,等.针灸预处理对大鼠心肌缺血再灌注后内质网应激的影响[J].中华危重症医学杂志(电子版),2014,7(3):172-175.
[33]RIEUSSET J.Mitochondria and endoplasmic reticulum:mitochondria-endoplasmic reticulum interplay in type 2diabetes pathophysiology[J].Int J Biochem Cell Biol,2011,43(9):1257-1262.
[34]袁爱红,查必祥,吴吉萍,等.针刺对糖尿病大鼠胰腺内质网应激PERK-CHOP途径与Bax/Bcl-2基因表达的影响[J].中华中医药杂志,2017,32(3):1291-1294.
[35]邵俊,查必祥,袁爱红,等.电针对糖尿病大鼠胰腺组织CHOP、Bax、Bcl-2蛋白表达及胰腺超微结构的影响[J].安徽中医药大学学报,2015,34(6):501-504.
[36]张毅,唐成林,田源,等.电针对非酒精性脂肪性肝病大鼠蛋白质二硫化物异构酶A3的影响[J].四川大学学报(医学版),2016,47(2):208-213.
[37]张毅,唐成林,田源,等.电针联合饮食调控对非乙醇性脂肪肝病大鼠肝脏内质网应激的影响[J].中国针灸,2016,36(9):951-956.
[38]余敏,李钢,唐成林,等.电针“丰隆”穴对非酒精性脂肪肝大鼠肝组织固醇调节元件结合蛋白-1c的影响[J].针刺研究,2017,42(4):308-314.
[39]丁海丽,孙竹昕,王海牛,等.大负荷运动及针刺干预对大鼠骨骼肌内质网应激钙信号的影响[J].北京体育大学学报,2017,40(11):49-55.