血瘀证的microRNA分子机制及中药干预作用
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摘要
microRNA是一类长约22个核苷酸的小分子非编码RNA,对基因表达具有转录后调控作用,因可同时调控多个靶基因,microRNA显示出广泛的生理作用,是多种疾病病理生理过程中的关键分子,也是药物治疗的新靶点。血瘀证主要特征表现为血液黏滞度增加、血小板黏附/聚集增强和微循环障碍,通常导致血管内皮功能不同程度受损。单个microRNA可调控多个靶基因表达,因而显示出多效性,呈现网络式调控作用,可能是现代中医药创新发展的突破点之一。目前研究显示,microRNA既是血瘀证诊断的重要客观参考,又是活血化瘀中药临床取效的重要作用靶点。应用现代医学新技术,研究microRNA在血瘀证患者辨病辨证中的临床应用可行性,从转录后水平寻找中医辨证诊断客观依据,探索microRNA与中医证型相关内在机制,可以提高临床辨证准确性,为治疗和改善预后提供更多干预目标,并为中医药理论发展提供更多支持。
MicroRNAs, a class of small molecular non-coding RNAs of 22 nucleotides,and it can regulate gene expression after transcription. Thus it can regulate. MicroRNA shows a wide range of physiological effects and it is a key molecule in the pathophysiological process of various diseases, and is also a new target for drug therapy. The main features of blood stasis syndrome are increased blood viscosity,platelet adhesion/aggregation,and microcirculatory disorders,which often result in impaired endothelial function. A single microRNA can regulate the expression of multiple target genes, thus showing pleiotropic effects and exhibiting network regulation. It may be one of the breakthroughs in the development of modern Chinese medicine innovation.
MicroRNAs, a class of small molecular non-coding RNAs of 22 nucleotides,and it can regulate gene expression after transcription. Thus it can regulate. MicroRNA shows a wide range of physiological effects and it is a key molecule in the pathophysiological process of various diseases, and is also a new target for drug therapy. The main features of blood stasis syndrome are increased blood viscosity,platelet adhesion/aggregation,and microcirculatory disorders,which often result in impaired endothelial function. A single microRNA can regulate the expression of multiple target genes, thus showing pleiotropic effects and exhibiting network regulation. It may be one of the breakthroughs in the development of modern Chinese medicine innovation.
引文
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[16]廖华君.降糖三黄片对糖尿病肾病microRNA-21信号通路的影响[D].广州:广州中医药大学,2017.
[17]袁洁,张军,戴金颖,等.益气养阴活血方对2型糖尿病大鼠胰腺miR-375表达水平和胰岛功能的影响[J].武警医学,2017,28(4):347-351.
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[22]张振鹏,滕菲,刘咏梅,等.丹参多酚酸盐干预非ST段抬高心肌梗死患者microRNA与靶基因[J].中国实验方剂学杂志,2017,23(19):17-22.
[23]熊婷婷,周健华,朱丹丹,等.血瘀证相关的microRNA-520b对白介素名的影响及丹参酮Ⅱ_A的干预作用[J].中国实验方剂学杂志,2015,21(10):113-117.
[24]李雪连,关会林,王璐,等丹参酮ⅡA调节microRNA-1保护缺氧心肌细胞的作用研究[J].现代生物医学进展,2014,14(28):5463-5467.
[25]冯俊,陈华文.丹参酮ⅡA通过调节miR-133水平对慢性心力衰竭心肌重构的影响[J].现代中西医结合杂志,2016,25(8):803-806.
[26]陈强,陈丽珠,郭晓华.丹参酮通过抑制miR-376b-5p逆转自发性高血压大鼠左室重构[J].中国老年学杂志,2016,36(22):5549-5551.
[27] DOWDY SF. Overcoming cellular barriers for RNA therapeutics[J]. Nat Biotechnol, 2017,35(3):222-229.
[28]中国中西医结合学会活血化瘀专业委员会.实用血瘀证诊断标准[J].中国中西医结合杂志,2016,36(10):1163.
[29]张敏州,陈可冀.急性心肌梗死中西医结合诊疗指南[J].中国中西医结合杂志,2018,38(3):272-284.
[30]郑思道,于雯,王宁元.MicroRNA介导的人参及其活性成分药理作用与机制[J].世界中西医结合杂志,2016,11(6):880-883.
[31]颜琳琳,周利红,李琦.中医血疲证动物模型研究概况[J].中医杂志,2014,55(3):255-258.
[32]吴德琳,刘宇娜,郑思道.心血管疾病运动康复新机制:microRNA的调控[J].中西医结合心脑血管病杂志,2017,15(21):2786-2789.
[2] CHEN R, CHEN M, XIAO Y, et al. Bioinformatics analysis of microRNAs related to blood stasis syndrome in diabetes mellitus patients[J]. Biosci Rep, 2018,38(2):BSR20171208.
[3] MELLIS D, CAPORAIL A. MicroRNA-based therapeutics in cardiovascular disease:screening and delivery to the target[J].Biochem Soc Trans, 2018,46(1):11-21.
[4] WOJCIECHOWSKA A, BRANIEWSKA A, KOZAR-KAMINSKAK. MicroRNA in cardiovascular biology and disease[J]. Adv Clin Exp Med, 2017,26(5):865-874.
[5] MATSUI M,COREY DR. Non-coding RNAs as drug targets[J].Nat Rev Drug Discov, 2017,16(3):167-179.
[6] CHEN C, PONNUSAMY M, LIU C, et al. MicroRNA as a Therapeutic Target in Cardiac Remodeling[J]. Biomed Res Int,2017,2017:1278436.
[7] WANG J, GUI Y. A Systems Biology Approach to Characterize Biomarkers for Blood Stasis Syndrome of Unstable Angina Patients by Integrating Micro RNA and Messenger RNA Expression Profiling[J]. Evidence-based complementary and alternative medicine:eCAM, 2013,2013:510208.
[8]廖江铨,王阶,刘咏梅,等.高通量测序筛选冠心病血瘀证相关IncRNA-miRNA-mRNA调控网络[J].中国实验方剂学杂志,2017,23(19):28-33.
[9]贾敏,蒋跃绒,苗阳,等.循环microRNA在急性冠脉综合征血瘀证轻重判别及预后评估中的意义[J].中国中西医结合杂志,2018,38(3):300-305.
[10] HOU J, WANG J, LIN C, et al. Circulating MicroRNA Profiles Differ between Qi-Stagnation and Qi-Deficiency in Coronary Heart Disease Patients with Blood Stasis Syndrome[J]. Evid Based Complement Altemat Med, 2014,2014:926962.
[11] WANG MM, FANG MX, CHEN LG, et al. Differential expression of microRNA in endothelial cells incubated with serum of hypertension patients with blood-stasis syndrome[J]. J Transl Med, 2015,21(11):817-822.
[12]黄守清,段利敏,尹莲花.血管内皮细胞miRNAs与高血压病血瘀证的相关性探讨[J].中国保健营养,2017,27(1):317.
[13]何铃,方梅霞,陈利国,等.高血压病血瘀证相关miRNA的筛选[J].中国病理生理杂志,2015,31(5):817-822.
[14] RUPAIMOOLE R, SLACK FJ. MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J].Nat Rev Drug Discov, 2017,16(3):203-222.
[15] YANG ZM, CHEN LH, HONG M, et al. Serum MicroRNA Profiling and Bioinformatics of Patients with Spleen-Deficiency Syndrome[J]. Evid Based Complement Alternat Med, 2016,2016:8726720.
[16]廖华君.降糖三黄片对糖尿病肾病microRNA-21信号通路的影响[D].广州:广州中医药大学,2017.
[17]袁洁,张军,戴金颖,等.益气养阴活血方对2型糖尿病大鼠胰腺miR-375表达水平和胰岛功能的影响[J].武警医学,2017,28(4):347-351.
[18]张军,刘颖,赵静,等.益气养阴活血方对2型糖尿病大鼠心肌微小基因miR-133a表达水平的影响[J].北京中医药大学学报,2017,40(3):226-231.
[19]王阶,滕菲,刘咏梅,等.血塞通对冠心病不稳定型心绞痛血瘀证患者microRNA的干预作用[J].中国实验方剂学杂志,2017,23(19):11-16.
[20]汪燕燕,郑思道,于雯. microRNA在糖尿病心血管损伤中的作用和意义[J].宁夏医学杂志,2013,35(2):185-188.
[21] YANG XR, TANG SM, YUAN QF, et al. Evaluating the effects of Danhong injection in treatment of acute ischemic stroke:study protocol for a multicenter randomized controlled trial[J]. Evid Based Complement Alternat Med, 2015,16:561.
[22]张振鹏,滕菲,刘咏梅,等.丹参多酚酸盐干预非ST段抬高心肌梗死患者microRNA与靶基因[J].中国实验方剂学杂志,2017,23(19):17-22.
[23]熊婷婷,周健华,朱丹丹,等.血瘀证相关的microRNA-520b对白介素名的影响及丹参酮Ⅱ_A的干预作用[J].中国实验方剂学杂志,2015,21(10):113-117.
[24]李雪连,关会林,王璐,等丹参酮ⅡA调节microRNA-1保护缺氧心肌细胞的作用研究[J].现代生物医学进展,2014,14(28):5463-5467.
[25]冯俊,陈华文.丹参酮ⅡA通过调节miR-133水平对慢性心力衰竭心肌重构的影响[J].现代中西医结合杂志,2016,25(8):803-806.
[26]陈强,陈丽珠,郭晓华.丹参酮通过抑制miR-376b-5p逆转自发性高血压大鼠左室重构[J].中国老年学杂志,2016,36(22):5549-5551.
[27] DOWDY SF. Overcoming cellular barriers for RNA therapeutics[J]. Nat Biotechnol, 2017,35(3):222-229.
[28]中国中西医结合学会活血化瘀专业委员会.实用血瘀证诊断标准[J].中国中西医结合杂志,2016,36(10):1163.
[29]张敏州,陈可冀.急性心肌梗死中西医结合诊疗指南[J].中国中西医结合杂志,2018,38(3):272-284.
[30]郑思道,于雯,王宁元.MicroRNA介导的人参及其活性成分药理作用与机制[J].世界中西医结合杂志,2016,11(6):880-883.
[31]颜琳琳,周利红,李琦.中医血疲证动物模型研究概况[J].中医杂志,2014,55(3):255-258.
[32]吴德琳,刘宇娜,郑思道.心血管疾病运动康复新机制:microRNA的调控[J].中西医结合心脑血管病杂志,2017,15(21):2786-2789.