针刺调控脑缺血再灌注损伤后内质网应激机制的研究进展
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摘要
脑缺血再灌注损伤(CIRI)是指缺血脑组织血供恢复再通后对脑组织及神经功能造成的二次损伤。内质网应激(ERS)是内质网受到外来压力刺激后大量错误及未折叠蛋白蓄积于内的现象。研究表明,CIRI可诱发ERS,而ERS又在CIRI的病理进程中发挥关键作用。一方面脑缺血再灌注后ERS可适度激活未折叠蛋白反应(UPR),促进内质网对错误折叠或未折叠蛋白进行处理,保护受损的神经细胞;另一方面持久剧烈的UPR则会进一步激活细胞的程序性死亡途径,诱发细胞自噬和细胞凋亡。越来越多的研究表明,针刺对大鼠脑缺血再灌注后诱导的内质网应激反应以及过度的内质网应激后引发的神经细胞自噬和凋亡均有一定的影响。因此,本研究对针刺调控CIRI后ERS的相关机制的研究进展进行概述,以期为临床应用针刺防治缺血性卒中提供一定的科学依据。
Cerebral ischemia-reperfusion injury( CIRI) refers to the secondary damage caused by brain tissue and nerve function after the blood supply of ischemic brain tissue is restored. Endoplasmic reticulum stress( ERS) is a phenomenon in which a large number of errors and unfolded proteins accumulate in the endoplasmic reticulum after being stimulated by external stress. Studies have shown that CIRI can induce ERS,and ERS plays a key role in the pathological process of CIRI. On one hand,ERS can moderately activate unfolded protein response( UPR) after cerebral ischemia-reperfusion( CIR),promote endoplasmic reticulum to treat misfolded or unfolded proteins,and protect damaged nerve cells; on the other hand,long-lasting and vigorous UPR will further activate the programmed cell death pathway,induce autophagy and apoptosis. Acupuncture has certain effects on ERS induced by CIR in rats,as well as on autophagy and neuronal apoptosis induced by excessive ERS. This study summarized the research progress of acupuncture on the mechanism of ERS after CIRI,thus to provide a scientific basis for clinical application of acupuncture preventing ischemic stroke.
Cerebral ischemia-reperfusion injury( CIRI) refers to the secondary damage caused by brain tissue and nerve function after the blood supply of ischemic brain tissue is restored. Endoplasmic reticulum stress( ERS) is a phenomenon in which a large number of errors and unfolded proteins accumulate in the endoplasmic reticulum after being stimulated by external stress. Studies have shown that CIRI can induce ERS,and ERS plays a key role in the pathological process of CIRI. On one hand,ERS can moderately activate unfolded protein response( UPR) after cerebral ischemia-reperfusion( CIR),promote endoplasmic reticulum to treat misfolded or unfolded proteins,and protect damaged nerve cells; on the other hand,long-lasting and vigorous UPR will further activate the programmed cell death pathway,induce autophagy and apoptosis. Acupuncture has certain effects on ERS induced by CIR in rats,as well as on autophagy and neuronal apoptosis induced by excessive ERS. This study summarized the research progress of acupuncture on the mechanism of ERS after CIRI,thus to provide a scientific basis for clinical application of acupuncture preventing ischemic stroke.
引文
[1]郎丰山,黄云霞,薛云,等.脑缺血再灌注损伤病理生理机制研究进展[J].食品与药品,2018,20(4):312-316.
[2]宋乐乐,刘浩,蒋琛琛.内质网应激与自噬信号通路研究进展[J].蚌埠医学院学报,2014,39(5):687-690.
[3]李欲轲,熊孟连,徐僡,等.内质网应激与凋亡研究进展[J].分子植物育种,2018,16(23):7856-7862.
[4]Nakka VP,Gusain A,Raghubir R.Endoplasmicreticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats[J].NeurotoxRes,2010,17(2):189-202.
[5]舒适.针刺干预内质网应激调节脑缺血再灌注大鼠神经细胞自噬的机制研究[D].上海:第二军医大学,2017.
[6]Lai CW,Aronson DE,Lee ES.Bi Pavailability distinguishes states of homeostasis and stress in the endoplasmic reticulum of living cells[J].Mol Biol Cell,2010,21(12):1909-1921.
[7]张翼飞,郑辑英,李东芳,等.内质网应激与脑缺血再灌注损伤研究进展[J].临床医药实践,2017,26(5):384-387.
[8]Singh AK,Singh S,Tripathi VK,et al.Rapamycin confers neuroprotection againgst aging-induced oxidative stress,mitochondrial dysfunction and neurodegeneration in old rats via activation of autophagy[J].Rejunvenation Res,2018,PMID:29943667.
[9]高玲莉,冯晓东.电针神庭、百会穴对脑缺血再灌注后认知障碍大鼠学习记忆能力及自噬相关基因和蛋白表达的影响[J].康复学报,2016,26(4):17-22.
[10]Krebs J,Agellon LB,Michalak M.Ca2+homeostasis and endoplasmic reticulum(ER)stress:An integrated view of calcium signaling[J].Biophys Res Commun,2015,460(1):114-121.
[11]吕哲,张颖,时美娟,等.内质网应激对大鼠局灶性脑缺血再灌注后听皮层损伤的作用[J].重庆医学,2018,47(11):1440-1443,1448.
[12]刘鸿涛.缺血后处理对心肌缺血再灌注损伤大鼠内质网应激相关蛋白葡萄糖调节蛋白78及半胱氨酸天冬氨酸蛋白酶-12的影响[J].中国老年学杂志,2018,38(12):3038-3040.
[13]Liu XR,Zhao SF,Liu F,et al.Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis[J].Stroke,2014,5(6):692-700.
[14]Yang JW,Hu ZP.Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress[J].Neural Regeneration Research,2015,10(8):1239-1244.
[15]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表达的影响[J].中国针灸,2014,34(9):889-893.
[16]Shen J,Lei XM,Song Y,et al.Electro-acupuncture on Nei Guan and Bai Hui:How Does It Affect GRP78 and Caspase-12 Gene Expression in Rats with Ischemia-Reperfusion Injury[J].Journal of Acupuncture&Herbs,2015,3(1):65-69.
[17]屈生彪,王勇.内质网应激在脑缺血再灌注损伤中作用[J].华夏医学,2018,31(1):170-174.
[18]齐文涛,曹德茂,彭爱军,等.内质网应激与蛛网膜下腔出血后早期脑损伤的相关性研究[J].医学研究杂志,2018,47(8):154-159.
[19]刘江.内质网应激蛋白ATF6-CHOP在肝脏缺血再灌注损伤中对细胞焦亡的调控机制研究[D].泸州:西南医科大学,2018.
[20]李翡翡.辐射通过内质网应激诱导CHOP和JNK的表达对乳腺癌细胞自噬和凋亡的调节机制研究[D].兰州:中国科学院(近代物理研究所),2016.
[21]Dhanasekaran DN,Reddy EP.JNK signaling in apopto sis[J].Oncogene,2008,27:6245-6251.
[22]张亚敏.电针百会、足三里穴对脑缺血再灌注大鼠内质网应激通路影响的研究[D].北京:北京协和医学院,2017.
[23]宋洋.针刺对MCAO大鼠内质网应激PKRK凋亡通路的影响[D].长沙:湖南中医药大学,2013.
[24]李文慧.电针百会、内关对脑缺血再灌注大鼠内质网应激GRP78和CHOP基因表达的影响[D].长沙:湖南中医药大学,2016.
[25]余琴华,于涛,徐建永,等.电针对脑缺血再灌注大鼠内质网应激关键因子GRP-78、Caspase-12表达的影响[J].中国中西医结合杂志,2018,38(5):579-585.
[26]王海英,亚白柳,王文淼,等.电针对脑缺血-再灌注损伤大鼠运动功能的改善作用及机制研究[J].济宁医学院学报,2018,41(5):313-316,321.
[27]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].湖南中医药大学学报,2016,36(2):54-57.
[28]Wei K,Wang P,Miao CH.A double edged sword with the rapeutic potential:an updated role of autophagy in ischemic cerebral injury[J].CNS Neurosci ther,2012,18(11):879-886.
[29]Cebollero E,Reggiori F,Kraft C.Reticulophagy and ribophagy:regulated degradation of protein production factories[J].InternatJ Cell Biol,2012,2012:182834.
[30]黄倩倩,温彬宇,闫妍,等.内质网应激和自噬的交互作用及其在阿尔茨海默病进展与防治中的作用[J].中国药理学通报,2018,34(11):1500-1504.
[31]Kusano M,Zai H,Hosaka H,et al.New frontiers in gut nutrient sensor research:monoso-dium L-glutamate added to a high-energy,high-protein liquid diet promotes gastric emptying:a possible therapy for patients with functional dyspepsia[J].J Pharmacol Sci,2010,34(112):33-36.
[32]张冰缘,马丽丽,朱琳,等.自噬在缺血再灌注损伤中的研究现状[J].世界最新医学信息文摘,2017,17(26):65-66,68.
[33]陈颖霞.脑缺血过程中自噬作用的研究进展[J].中国动脉硬化杂志,2016,24(6):644.
[34]Shen S,Zhang Y,Zhang R,et al.Ursolic acid induces autophagy in U87MG cells via ROS-dependent endoplasmic reticulum stress[J].Chem Biol Interact,2014,218:28-41
[35]王晓茹,安芳.自噬及其在脑缺血再灌注损伤中作用机制[J].神经药理学报,2016,6(1):41-48.
[36]薛卫国,张忠,许红,等.电针对APP转基因鼠神经元自噬途径的影响[J].针刺研究,2014,39(4):272-277.
[37]赵伟,刘延祥,王占魁,等.自噬对电针治疗大鼠实验性坐骨神经损伤后神经再生的影响[J].天津中医药大学学报,2014,33(6):351-354.
[38]冯晓东,王慧灵,陈卓,等.自噬在脑卒中后认知障碍中的作用研究[J].时珍国医国药,2017,28(7):1730-1732.
[39]徐勤红,彭拥军.“通督调神针法”治疗急性脑梗死临床疗效观察及其对自噬的影响[J].中国针灸,2018,38(5):457-461.
[40]冯晓东,高玲莉,李瑞青,等.电针对脑缺血再灌注模型大鼠脑组织Beclin-1蛋白及基因表达的影响[J].中国康复医学杂志,2016,31(12):1307-1310.
[2]宋乐乐,刘浩,蒋琛琛.内质网应激与自噬信号通路研究进展[J].蚌埠医学院学报,2014,39(5):687-690.
[3]李欲轲,熊孟连,徐僡,等.内质网应激与凋亡研究进展[J].分子植物育种,2018,16(23):7856-7862.
[4]Nakka VP,Gusain A,Raghubir R.Endoplasmicreticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats[J].NeurotoxRes,2010,17(2):189-202.
[5]舒适.针刺干预内质网应激调节脑缺血再灌注大鼠神经细胞自噬的机制研究[D].上海:第二军医大学,2017.
[6]Lai CW,Aronson DE,Lee ES.Bi Pavailability distinguishes states of homeostasis and stress in the endoplasmic reticulum of living cells[J].Mol Biol Cell,2010,21(12):1909-1921.
[7]张翼飞,郑辑英,李东芳,等.内质网应激与脑缺血再灌注损伤研究进展[J].临床医药实践,2017,26(5):384-387.
[8]Singh AK,Singh S,Tripathi VK,et al.Rapamycin confers neuroprotection againgst aging-induced oxidative stress,mitochondrial dysfunction and neurodegeneration in old rats via activation of autophagy[J].Rejunvenation Res,2018,PMID:29943667.
[9]高玲莉,冯晓东.电针神庭、百会穴对脑缺血再灌注后认知障碍大鼠学习记忆能力及自噬相关基因和蛋白表达的影响[J].康复学报,2016,26(4):17-22.
[10]Krebs J,Agellon LB,Michalak M.Ca2+homeostasis and endoplasmic reticulum(ER)stress:An integrated view of calcium signaling[J].Biophys Res Commun,2015,460(1):114-121.
[11]吕哲,张颖,时美娟,等.内质网应激对大鼠局灶性脑缺血再灌注后听皮层损伤的作用[J].重庆医学,2018,47(11):1440-1443,1448.
[12]刘鸿涛.缺血后处理对心肌缺血再灌注损伤大鼠内质网应激相关蛋白葡萄糖调节蛋白78及半胱氨酸天冬氨酸蛋白酶-12的影响[J].中国老年学杂志,2018,38(12):3038-3040.
[13]Liu XR,Zhao SF,Liu F,et al.Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis[J].Stroke,2014,5(6):692-700.
[14]Yang JW,Hu ZP.Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress[J].Neural Regeneration Research,2015,10(8):1239-1244.
[15]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表达的影响[J].中国针灸,2014,34(9):889-893.
[16]Shen J,Lei XM,Song Y,et al.Electro-acupuncture on Nei Guan and Bai Hui:How Does It Affect GRP78 and Caspase-12 Gene Expression in Rats with Ischemia-Reperfusion Injury[J].Journal of Acupuncture&Herbs,2015,3(1):65-69.
[17]屈生彪,王勇.内质网应激在脑缺血再灌注损伤中作用[J].华夏医学,2018,31(1):170-174.
[18]齐文涛,曹德茂,彭爱军,等.内质网应激与蛛网膜下腔出血后早期脑损伤的相关性研究[J].医学研究杂志,2018,47(8):154-159.
[19]刘江.内质网应激蛋白ATF6-CHOP在肝脏缺血再灌注损伤中对细胞焦亡的调控机制研究[D].泸州:西南医科大学,2018.
[20]李翡翡.辐射通过内质网应激诱导CHOP和JNK的表达对乳腺癌细胞自噬和凋亡的调节机制研究[D].兰州:中国科学院(近代物理研究所),2016.
[21]Dhanasekaran DN,Reddy EP.JNK signaling in apopto sis[J].Oncogene,2008,27:6245-6251.
[22]张亚敏.电针百会、足三里穴对脑缺血再灌注大鼠内质网应激通路影响的研究[D].北京:北京协和医学院,2017.
[23]宋洋.针刺对MCAO大鼠内质网应激PKRK凋亡通路的影响[D].长沙:湖南中医药大学,2013.
[24]李文慧.电针百会、内关对脑缺血再灌注大鼠内质网应激GRP78和CHOP基因表达的影响[D].长沙:湖南中医药大学,2016.
[25]余琴华,于涛,徐建永,等.电针对脑缺血再灌注大鼠内质网应激关键因子GRP-78、Caspase-12表达的影响[J].中国中西医结合杂志,2018,38(5):579-585.
[26]王海英,亚白柳,王文淼,等.电针对脑缺血-再灌注损伤大鼠运动功能的改善作用及机制研究[J].济宁医学院学报,2018,41(5):313-316,321.
[27]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].湖南中医药大学学报,2016,36(2):54-57.
[28]Wei K,Wang P,Miao CH.A double edged sword with the rapeutic potential:an updated role of autophagy in ischemic cerebral injury[J].CNS Neurosci ther,2012,18(11):879-886.
[29]Cebollero E,Reggiori F,Kraft C.Reticulophagy and ribophagy:regulated degradation of protein production factories[J].InternatJ Cell Biol,2012,2012:182834.
[30]黄倩倩,温彬宇,闫妍,等.内质网应激和自噬的交互作用及其在阿尔茨海默病进展与防治中的作用[J].中国药理学通报,2018,34(11):1500-1504.
[31]Kusano M,Zai H,Hosaka H,et al.New frontiers in gut nutrient sensor research:monoso-dium L-glutamate added to a high-energy,high-protein liquid diet promotes gastric emptying:a possible therapy for patients with functional dyspepsia[J].J Pharmacol Sci,2010,34(112):33-36.
[32]张冰缘,马丽丽,朱琳,等.自噬在缺血再灌注损伤中的研究现状[J].世界最新医学信息文摘,2017,17(26):65-66,68.
[33]陈颖霞.脑缺血过程中自噬作用的研究进展[J].中国动脉硬化杂志,2016,24(6):644.
[34]Shen S,Zhang Y,Zhang R,et al.Ursolic acid induces autophagy in U87MG cells via ROS-dependent endoplasmic reticulum stress[J].Chem Biol Interact,2014,218:28-41
[35]王晓茹,安芳.自噬及其在脑缺血再灌注损伤中作用机制[J].神经药理学报,2016,6(1):41-48.
[36]薛卫国,张忠,许红,等.电针对APP转基因鼠神经元自噬途径的影响[J].针刺研究,2014,39(4):272-277.
[37]赵伟,刘延祥,王占魁,等.自噬对电针治疗大鼠实验性坐骨神经损伤后神经再生的影响[J].天津中医药大学学报,2014,33(6):351-354.
[38]冯晓东,王慧灵,陈卓,等.自噬在脑卒中后认知障碍中的作用研究[J].时珍国医国药,2017,28(7):1730-1732.
[39]徐勤红,彭拥军.“通督调神针法”治疗急性脑梗死临床疗效观察及其对自噬的影响[J].中国针灸,2018,38(5):457-461.
[40]冯晓东,高玲莉,李瑞青,等.电针对脑缺血再灌注模型大鼠脑组织Beclin-1蛋白及基因表达的影响[J].中国康复医学杂志,2016,31(12):1307-1310.