杨惠茹,宋珊杉,易小莉,余军,许传铭
YANG Hui-ru,SONG Shan-shan,YI Xiao-li,YU Jun,XU Chuan-ming

• 1:江西中医药大学医学转化中心
• 2:天普大学LewisKatz医学院

摘要(Abstract)：

血管钙化是一个病变阶段，参与心血管疾病的发生发展过程，严重威胁着人类的生命健康安全，但目前临床上能够完全逆转或治愈血管钙化的药物屈指可数。血管钙化的发病机制主要涉及钙磷稳态失衡、细胞自噬障碍、内源性钙抑制丧失及内质网应激引起的细胞凋亡、炎症风暴、细胞成骨转分化和基质囊泡的释放。围绕“温经通脉，活血化瘀”和“补肾健脾，祛湿化浊”的治疗理念，大量中药单体/提取物及中药复方/中成药对血管钙化显示出很好的改善作用，但是它们的具体作用机制尚不明确，有待进一步的研究探索。该文系统地概括了血管钙化的发病机制，并总结了中药防治血管钙化的最新研究进展情况，为中药防治血管钙化的临床应用提供理论支持。
Vascular calcification is a pathological stage involved in the occurrence and development of cardiovascular diseases, seriously threatening human life and health. At present, few drugs can completely reverse or cure vascular calcification in clinical practice. The pathogenesis of vascular calcification mainly involves the disturbance of calcium and phosphorus homeostasis, autophagy dysfunction, loss of endogenous calcium inhibition, and the apoptosis, cytokine storm, cell osteoblastic transdifferentiation, and stromal vesicle release induced by endoplasmic reticulum stress. Following the therapeutic concepts of warming channels and dredging vessels, activating blood and resolving stasis, tonifying kidney and invigorating spleen, and removing dampness and eliminating turbid, a large number of traditional Chinese medicine(TCM) active compounds/extracts and TCM prescriptions/Chinese patent medicines have shown satisfactory performance in treating vascular calcification, while the specific mechanisms remain unclear and awaits further investigations. This article systematically summarized the pathogenesis of vascular calcification and the latest research progress of TCM in the prevention and treatment of vascular calcification, providing theoretical support for the clinical application of TCM in the prevention and treatment of vascular calcification.

关键词(KeyWords)： 血管钙化;中药;钙磷稳态;成骨转分化;内质网应激;细胞自噬;细胞凋亡
vascular calcification;traditional Chinese medicine;calcium and phosphorus homeostasis;osteogenic transdifferentiation;endoplasmic reticulum stress;autophagy;apoptosis

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(82160051,32100908);; 江西省“双千计划”项目(jxsq2020101074);; 江西省自然科学基金项目(20232BAB206018);; 江西省教育厅科技项目(GJJ2200904);; 江西中医药大学中西医结合一级学科(江西省双一流学科)项目(zxyylxk20220103)

作者(Author): 杨惠茹,宋珊杉,易小莉,余军,许传铭
YANG Hui-ru,SONG Shan-shan,YI Xiao-li,YU Jun,XU Chuan-ming

DOI: 10.19540/j.cnki.cjcmm.20240422.601

参考文献(References)：

• [1] ROCHA-SINGH K J,ZELLER T,JAFF M R,Peripheral arterial calcification:prevalence,mechanism,detection,and clinical implications[J].Catheter Cardiovasc Interv,2014,83(6):E212.
• [2] GIACHELLI C M.Vascular calcification mechanisms[J].J Am Soc Nephrol,2004,15(12):2959.
• [3] GIACHELLI C M.Mechanisms of vascular calcification in uremia[J].Semin Nephrol,2004,24(5):401.
• [4] ZHANG H,LI G,YU X,et al.Progression of vascular calcification and clinical outcomes in patients receiving maintenance dialysis[J].JAMA Netw Open,2023,6(5):e2310909.
• [5] LIU Z H,YU X Q,YANG J W,et al.Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis:baseline results from a prospective cohort study[J].Curr Med Res Opin,2018,34(8):1491.
• [6] BELLASI A,KOOIENGA L,BLOCK G A,et al.How long is the warranty period for nil or low coronary artery calcium in patients new to hemodialysis?[J].J Nephrol,2009,22(2):255.
• [7] FAGGIANO P,DASSENI N,GAIBAZZI N,et al.Cardiac calcification as a marker of subclinical atherosclerosis and predictor of cardiovascular events:a review of the evidence[J].Eur J Prev Cardiol,2019,26(11):1191.
• [8] FAGGIANO A,SANTANGELO G,CARUGO S,et al.Cardiovascular calcification as a marker of increased cardiovascular risk and a surrogate for subclinical atherosclerosis:role of echocardiography[J].J Clin Med,2021,10(8):1668.
• [9] 刘文娟，姜晨.基于“治未病”思想探讨慢性肾脏病血管钙化的危险因素及中医药防治措施[J].中国现代医生，2021,59(33):35.
• [10] 王岚，王平，邹新蓉，等.从“肾藏精主骨”理论探讨中医药治疗CKD骨-血管轴病变的机理[J].时珍国医国药，2020,31(2):385.
• [11] WU M,REMENTER C,GIACHELLI C M.Vascular calcification:an update on mechanisms and challenges in treatment[J].Calcif Tissue Int,2013,93(4):365.
• [12] DOHERTY T M,ASOTRA K,FITZPATRICK L A,et al.Calcification in atherosclerosis:bone biology and chronic inflammation at the arterial crossroads[J].Proc Natl Acad Sci USA,2003,100(20):11201.
• [13] ROIJERS R B,DEBERNARDI N,CLEUTJENS J P,et al.Microcalcifications in early intimal lesions of atherosclerotic human coronary arteries[J].Am J Pathol,2011,178(6):2879.
• [14] CIANCIOLO G,CAPELLI I,CAPPUCCILLI M,et al.Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?[J] Clin Kidney J,2017,10(3):389.
• [15] THOMPSON B,TOWLER D A.Arterial calcification and bone physiology:role of the bone-vascular axis[J].Nat Rev Endocrinol,2012,8(9):529.
• [16] REN X,LI F,WANG C,et al.Age- and sex-related aortic valve dysfunction and aortopathy difference in patients with bicuspid aortic valve[J].Int Heart J,2019,60(3):637.
• [17] SHEKAR C,BUDOFF M.Calcification of the heart:mechanisms and therapeutic avenues[J].Expert Rev Cardiovasc Ther,2018,16(7):527.
• [18] YANG H,CURINGA G,GIACHELLI C M.Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro[J].Kidney Int,2004,66(6):2293.
• [19] REYNOLDS J L,JOANNIDES A J,SKEPPER J N,et al.Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations:a potential mechanism for accelerated vascular calcification in ESRD[J].J Am Soc Nephrol,2004,15(11):2857.
• [20] ABBASIAN N.Vascular calcification mechanisms:updates and renewed insight into signaling pathways involved in high phosphate-mediated vascular smooth muscle cell calcification[J].Biomedicines,2021,9(7):804.
• [21] LI T,YU H,ZHANG D,et al.Matrix vesicles as a therapeutic target for vascular calcification[J].Front Cell Dev Biol,2022,10:825622.
• [22] JONO S,MCKEE M D,MURRY C E,et al.Phosphate regulation of vascular smooth muscle cell calcification[J].Circ Res,2000,87(7):E10.
• [23] DUAN X,ZHOU Y,TENG X,et al.Endoplasmic reticulum stress-mediated apoptosis is activated in vascular calcification[J].Biochem Biophys Res Commun,2009,387(4):694.
• [24] VILLA-BELLOSTA R,EGIDO J.Phosphate,pyrophosphate,and vascular calcification:a question of balance[J].Eur Heart J,2017,38(23):1801.
• [25] LI W,CAO T,LUO C,et al.Crosstalk between ER stress,NLRP3 inflammasome,and inflammation[J].Appl Microbiol Biotechnol,2020,104(14):6129.
• [26] WEN C,YANG X,YAN Z,et al.Nalp3 inflammasome is activated and required for vascular smooth muscle cell calcification[J].Int J Cardiol,2013,168(3):2242.
• [27] MASUDA M,MIYAZAKI-ANZAI S,KEENAN A L,et al.Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells[J].JCI Insight,2016,1(18):e88646.
• [28] SAITO A,OCHIAI K,KONDO S,et al.Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2 [J].J Biol Chem,2011,286(6):4809.
• [29] DUAN X H,CHANG J R,ZHANG J,et al.Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification [J].Apoptosis,2013,18(9):1132.
• [30] LIBERMAN M,JOHNSON R C,HANDY D E,et al.Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification [J].Biochem Biophys Res Commun,2011,413(3):436.
• [31] HUTCHESON J D,GOETTSCH C,BERTAZZO S,et al.Genesis and growth of extracellular-vesicle-derived microcalcifica-tion in atherosclerotic plaques [J].Nat Mater,2016,15(3):335.
• [32] RAO Z,ZHENG Y,XU L,et al.Endoplasmic reticulum stress and pathogenesis of vascular calcification [J].Front Cardiovasc Med,2022,9:918056.
• [33] LEE S J,LEE I K,JEON J H.Vascular calcification-new insights into its mechanism [J].Int J Mol Sci,2020,21(8):2685.
• [34] ZEINI M,LOPEZ-FONTAL R,TRAVES P G,et al.Differential sensitivity to apoptosis among the cells that contribute to the atherosclerotic disease [J].Biochem Biophys Res Commun,2007,363(2):444.
• [35] PROUDFOOT D,SKEPPER J N,HEGYI L,et al.Apoptosis regulates human vascular calcification in vitro:evidence for initiation of vascular calcification by apoptotic bodies [J].Circ Res,2000,87(11):1055.
• [36] DURHAM A L,SPEER M Y,SCATENA M,et al.Role of smooth muscle cells in vascular calcification:implications in atherosclerosis and arterial stiffness [J].Cardiovasc Res,2018,114(4):590.
• [37] SHI Y,WANG S,PENG H,et al.Fibroblast growth factor 21 attenuates vascular calcification by alleviating endoplasmic reticulum stress mediated apoptosis in rats [J].Int J Biol Sci,2019,15(1):138.
• [38] FURMANIK M,VAN GORP R,WHITEHEAD M,et al.Endoplasmic reticulum stress mediates vascular smooth muscle cell calcification via increased release of Grp78 (glucose-regulated protein,78 kDa)-loaded extracellular vesicles [J].Arterioscler Thromb Vasc Biol,2021,41(2):898.
• [39] SHI Y,LU W,HOU Y,et al.Fibroblast growth factor 21 ameliorates vascular calcification by inhibiting osteogenic transition in vitamin D3 plus nicotine-treated rats [J].Biochem Biophys Res Commun,2018,495(4):2448.
• [40] DEMER L L,TINTUT Y.Inflammatory,metabolic,and genetic mechanisms of vascular calcification [J].Arterioscler Thromb Vasc Biol,2014,34(4):715.
• [41] ABDELBAKY A,CORSINI E,FIGUEROA A L,et al.Focal arterial inflammation precedes subsequent calcification in the same location:a longitudinal FDG-PET/CT study [J].Circ Cardiovasc Imaging,2013,6(5):747.
• [42] AIKAWA E,NAHRENDORF M,FIGUEIREDO J L,et al.Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo [J].Circulation,2007,116(24):2841.
• [43] IWASAKI Y,SUGANAMI T,HACHIYA R,et al.Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages [J].Diabetes,2014,63(1):152.
• [44] HAO N,ZHOU Z,ZHANG F,et al.Interleukin-29 accelerates vascular calcification via JAK2/STAT3/BMP2 signaling [J].J Am Heart Assoc,2023,12(1):e027222.
• [45] KAPUSTIN A N,DAVIES J D,REYNOLDS J L,et al.Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization [J].Circ Res,2011,109(1):e1.
• [46] SHROFF R C,MCNAIR R,SKEPPER J N,et al.Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification [J].J Am Soc Nephrol,2010,21(1):103.
• [47] NEW S E,GOETTSCH C,AIKAWA M,et al.Macrophage-derived matrix vesicles:an alternative novel mechanism for microcalcification in atherosclerotic plaques [J].Circ Res,2013,113(1):72.
• [48] LEROYER A S,ISOBE H,LESECHE G,et al.Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques [J].J Am Coll Cardiol,2007,49(7):772.
• [49] KAPUSTIN A N,CHATROU M L,DROZDOV I,et al.Vascular smooth muscle cell calcification is mediated by regulated exosome secretion [J].Circ Res,2015,116(8):1312.
• [50] YANG W,ZOU B,HOU Y,et al.Extracellular vesicles in vascular calcification [J].Clin Chim Acta,2019,499:118.
• [51] PHADWAL K,FENG D,ZHU D,et al.Autophagy as a novel therapeutic target in vascular calcification [J].Pharmacol Ther,2020,206:107430.
• [52] NAKAMURA S,YOSHIMORI T.Autophagy and longevity [J].Mol Cells,2018,41(1):65.
• [53] DAI X Y,ZHAO M M,CAI Y,et al.Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release [J].Kidney Int,2013,83(6):1042.
• [54] HSU Y J,HSU S C,HUANG S M,et al.Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling [J].J Vasc Surg,2015,62(1):210.
• [55] MORCIANO G,PATERGNANI S,PEDRIALI G,et al.Impairment of mitophagy and autophagy accompanies calcific aortic valve stenosis favouring cell death and the severity of disease [J].Cardiovasc Res,2022,118(11):2548.
• [56] MONTEZANO A C,ZIMMERMAN D,YUSUF H,et al.Vascular smooth muscle cell differentiation to an osteogenic phenotype involves TRPM7 modulation by magnesium[J].Hypertension,2010,56(3):453.
• [57] ZEBBOUDJ A F,IMURA M,BOSTROM K.Matrix GLA protein,a regulatory protein for bone morphogenetic protein-2[J].J Biol Chem,2002,277(6):4388.
• [58] HRUSKA K A,MATHEW S,SAAB G.Bone morphogenetic proteins in vascular calcification[J].Circ Res,2005,97(2):105.
• [59] MEHROTRA R.Emerging role for fetuin-A as contributor to morbidity and mortality in chronic kidney disease[J].Kidney Int,2007,72(2):137.
• [60] 刘洁.温阳活血法对高磷诱导兔主动脉平滑肌细胞钙化的影响[D].南宁：广西中医药大学，2018.
• [61] 钟建，唐农，史伟，等.温阳通络泄浊方对维持性血液透析患者血管钙化的影响[J].中医杂志，2016,57(7):588.
• [62] RANGASWAMI J,BHALLA V,BLAIR J E A,et al.Cardiorenal syndrome:classification,pathophysiology,diagnosis,and treatment strategies:a scientific statement from the american heart association[J].Circulation,2019,139(16):e840.
• [63] RONCO C,HAAPIO M,HOUSE A A,et al.Cardiorenal syndrome[J].J Am Coll Cardiol,2008,52(19):1527.
• [64] 黄玮玮.益肾排浊方治疗慢性肾脏病肾虚湿浊证的疗效观察及对血清FGF23和Klotho蛋白的影响[D].南京：南京中医药大学，2019.
• [65] 范桢亮.祛瘀化浊汤治疗CKD-Ⅳ期湿浊瘀血证伴血管钙化的临床观察[D].哈尔滨：黑龙江中医药大学，2017.
• [66] 马筱璠.陈氏肾复汤对脾肾气虚、湿浊瘀阻型慢性肾脏病(CKD3a期)患者的疗效观察及对血清胎球蛋白A的影响[D].福州：福建中医药大学，2020.
• [67] 詹指南.滋肾降浊汤对脾肾气阴两虚夹瘀证慢性肾脏病(CKD4期)患者临床疗效及血清FGF23、Klotho蛋白的影响[D].福州：福建中医药大学，2022.
• [68] 孙钠.川芎嗪抑制大鼠血管钙化及其机制研究[J].医药导报，2013,32(4):418.
• [69] 李恩刚.银杏叶提取物对高磷诱导的慢性肾脏病大鼠血管钙化作用的研究[D].济南：山东大学，2016.
• [70] 韩怡然.羟基红花黄色素A延缓高磷诱导的血管平滑肌细胞钙化及其机制研究[D].沈阳：中国医科大学，2020.
• [71] 付尧，吴冬冬，李晓东.姜黄素对维生素D3和尼古丁诱导血管钙化大鼠血管中组织蛋白酶D表达的影响[J].中国动脉硬化杂志，2018,26(5):485.
• [72] 李芬芬，尹忠诚，张颖.水蛭素对高磷诱导的大鼠血管平滑肌细胞钙化的影响[J].中国现代应用药学，2020,37(24):2945.
• [73] 钟慧，李带瑛，王苏樱，等.丹参酮Ⅱa通过NF-κB和β-catenin信号通路抑制血管钙化[J].生理学报，2022,74 (6):949.
• [74] 苏保林，陈刚毅，李敬.丹参酮胶囊对糖尿病肾病患者成纤维细胞生长因子23-Klotho轴及血管钙化的影响[J].云南中医学院学报，2016,39(2):11.
• [75] 李彬，尹慧君.丹参多酚酸盐对大鼠血管平滑肌细胞钙化的抑制作用[J].武警医学，2013,24(7):580.
• [76] 张杰，王少敏，刘敏，等.丹参素对血管平滑肌细胞钙化和凋亡的抑制作用[J].中国医院药学杂志，2019,39(18):1857.
• [77] 林评兰，吴明，杨枫，等.丹酚酸B激活自噬改善高磷诱导血管平滑肌细胞钙化的机制研究[J].中国医院药学杂志，2022,42(12):1192.
• [78] 韩锦，姚智会，马晓桃，等.海藻异枝麒麟菜多糖对纳米羟磷灰石晶体损伤小鼠血管平滑肌细胞的影响[J].中国医药导报，2019,16(33):4.
• [79] 刘国栋.白藜芦醇抑制维生素D3和尼古丁诱导大鼠血管钙化的作用及机制研究[D].北京：中国人民解放军医学院，2015.
• [80] 张宜华.白藜芦醇抑制AGEs诱导泡沫细胞形成及血管平滑肌细胞钙化的机制研究[D].重庆：第三军医大学，2010.
• [81] 张明慧，王本泉，蔡晓青，等.白藜芦醇抑制血管平滑肌细胞成骨样转化的实验研究[J].中草药，2014,45(10):1444.
• [82] 施晴波.白藜芦醇减轻高磷诱导的离体大鼠主动脉环钙化的研究[D].南京：南京医科大学，2018.
• [83] 袁秀.白藜芦醇对LPS诱导的人血管平滑肌细胞炎症及成骨反应的调节作用及其机制探讨[D].广州：南方医科大学，2018.
• [84] MANIVANNAN J,BARATHKUMAR T R,SIVASUBRAMA-NIAN J,et al.Diosgenin attenuates vascular calcification in chronic renal failure rats[J].Mol Cell Biochem,2013,378(1/2):9.
• [85] LU X,LIU X,LIANG E,et al.Panax quinquefolius saponin inhibits vascular smooth muscle cell calcification via activation of nuclear factor-erythroid 2-related factor 2[J].BMC Complement Med Ther,2023,23(1):129.
• [86] ZHOU Z,LI Y,JIANG W,et al.Molecular mechanism of calycosin inhibited vascular calcification[J].Nutrients,2023,16(1):99.
• [87] 陈艳，汪雄，彭吉霞，等.黄芪皂苷在大鼠血管钙化中的作用及可能机制[J].广东医学，2011,32(7):824.
• [88] NANAO-HAMAI M,SON B K,KOMURO A,et al.Ginsenoside Rb1 inhibits vascular calcification as a selective androgen receptor modulator[J].Eur J Pharmacol,2019,859:172546.
• [89] ZHOU P,ZHANG X,GUO M,et al.Ginsenoside Rb1 ameliorates CKD-associated vascular calcification by inhibiting the Wnt/beta-catenin pathway[J].J Cell Mol Med,2019,23(10):7088.
• [90] 胡艳红，杨静，修成奎，等.人参-三七-川芎提取物延缓高糖诱导的小鼠血管钙化的机制[J].中国实验方剂学杂志，2020,26(8):13.
• [91] 林基伟，刘新辉，吴海滨，等.黄芪-丹参配伍对腺嘌呤诱导慢性肾功能衰竭大鼠心血管钙化的影响[J].广州中医药大学学报，2019,36(3):385.
• [92] 毛稼琦，马兰，刘川川，等.红景天苷抑制低氧诱导的大鼠肺动脉平滑肌细胞的表型转化[J].中国中药杂志，2022,47(4):1024.
• [93] 张彦燕，何丽，涂梦欣，等.红景天苷下调BMP2/Smad1信号抑制血管平滑肌细胞表型转化的作用[J].西南民族大学学报(自然科学版),2020,46(6):595.
• [94] 陈慧敏，刘思齐，左风云，等.降脂宁提取物对血管钙化的影响及其机制[J].中国医药导报，2016,13(33):25.
• [95] LU L,LI Y,DONG Q,et al.Wogonin inhibits oxidative stress and vascular calcification via modulation of heme oxygenase-1[J].Eur J Pharmacol,2023,958:176070.
• [96] 张旭慧.小檗碱对血管平滑肌细胞钙化的影响及其机制初探[D].石家庄：河北医科大学，2018.
• [97] 段书众，于文会，张华，等.小檗碱通过PERK-ATF4通路对高糖诱导的血管平滑肌细胞钙化的改善作用[J].中成药，2022,44(10):3325.
• [98] LI L,ZHENG G,CAO C,et al.The ameliorative effect of berberine on vascular calcification by inhibiting endoplasmic reticulum stress[J].J Cardiovasc Pharmacol,2022,80(2):294.
• [99] 张鑫鹏，曾存良，孙晓磊，等.黄连素对人主动脉血管平滑肌细胞钙化的作用及其机制[J].山东医药，2018,58(33):1.
• [100] 曾存良，张鑫鹏，胥雄飞，等.黄连素对糖尿病大鼠血管钙化的影响及其机制研究[J].现代中西医结合杂志，2019,28(8):799.
• [101] 高帅，泮思林，杜占慧，等.地黄多糖抑制大鼠主动脉血管钙化的实验研究[J].中华实验外科杂志，2021,38(8):1466.
• [102] 乔洁，李怡，杨黎，等.改构黄藤素对钙化细胞的作用机制[J].四川大学学报(自然科学版),2018,55(6):1319.
• [103] 王恬，吴海，徐华，等.氧化苦参碱对大鼠血管平滑肌细胞钙化抑制作用的研究[J].宁夏医学院学报，2008,30(3):277.
• [104] 王秀梅，张娟，张鸣号，等.氧化苦参碱对人脐静脉平滑肌细胞钙化的影响及其可能机制[J].中国中药杂志，2012,37(7):1002.
• [105] 白晓君，刘艳，郜珊珊，等.淫羊藿苷抑制氧化应激诱导主动脉血管平滑肌细胞钙化的机制研究[J].中国中药杂志，2021,46(17):4497.
• [106] 任璐，王尊，华清钟，等.淫羊藿素预防小鼠血管钙化[J].中南大学学报(医学版),2019,44(1):35.
• [107] HE H Q,LAW B Y K,ZHANG N,et al.Bavachin protects human aortic smooth muscle cells against beta-glycerophosphate-mediated vascular calcification and apoptosis via activation of mTOR-dependent autophagy and suppression of beta-catenin signaling[J].Front Pharmacol,2019,10:1427.
• [108] 邱小波.虫草菌液通过增强自噬改善β-甘油磷酸诱导的血管平滑肌细胞钙化[D].沈阳：中国医科大学，2019.
• [109] 梁英权，韩际宏，余茂耘.霍山石斛对高脂诱导的LDLR基因敲除小鼠动脉粥样硬化和血管钙化的影响[J].中国动脉硬化杂志，2020,28(11):930.
• [110] JIANG W,RUAN W,WANG Z.Dendrobium officinale polysaccharide inhibits vascular calcification via anti-inflammatory and anti-apoptotic effects in chronic kidney disease[J].FASEB J,2022,36(9):e22504.
• [111] 邵静，陈安，张秀丽，等.吴茱萸次碱通过Sirt1改善血管平滑肌细胞钙化[J].中山大学学报(医学版),2019,40(3):387.
• [112] 陈燕亭，宋艳，陆立鹤.附子多糖抑制血管平滑肌细胞钙化的神经酰胺机制[J].中山大学学报(医学版),2020,41(1):69.
• [113] LIAO L,ZHUANG X,LI W,et al.Polysaccharide from Fuzi protects against ox-LDL-induced calcification of human vascular smooth muscle cells by increasing autophagic activity[J].Mol Med Rep,2018,17(4):5109.
• [114] PEI Y Q,ZHENG Y Q,DING Y D,et al.Triptolide attenuates vascular calcification by upregulating expression of miRNA-204[J].Front Pharmacol,2020,11:581230.
• [115] YANG X,CHEN A,LIANG Q,et al.Up-regulation of heme oxygenase-1 by celastrol alleviates oxidative stress and vascular calcification in chronic kidney disease[J].Free Radic Biol Med,2021,172:530.
• [116] 徐华，纳春祥，李桂忠，等.表没食子儿茶素没食子酸酯减轻大鼠血管平滑肌细胞钙化的实验研究[J].宁夏医科大学学报，2010,32(6):660.
• [117] 田莹珺，袁博，梁涛.番茄红素抑制AGEs/RAGE信号通路对慢性肾功能衰竭大鼠血管钙化的影响[J].中国药师，2022,25(11):1898.
• [118] 韦婷婷.益肾排毒方对CKD4～5期非透析脾肾气虚兼浊瘀证患者钙磷代谢影响的临床观察[D].南宁：广西中医药大学，2022.
• [119] 柳诗意，张宁，孟祥飞，等.补肾活血方通过调节MGP、BMP-7因子对慢性肾脏病大鼠血管钙化的抑制作用[J].中国中西医结合肾病杂志，2018,19(8):672.
• [120] LIU S Y,MENG X F,LIU S W,et al.Effect of Bushen Huoxue decoction on inhibiting osteogenic differentiation of vascular smooth cells by regulating OPG/RANK/RANKL system in vascular calcification[J].Ann Transl Med,2019,7(6):125.
• [121] YANG C,XIE Z,LIU H,et al.Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification[J].Mol Med,2023,29(1):168.
• [122] 祝清秀，李映东.探讨通淋汤对尿毒症患者血管钙化因子表达及临床疗效影响[J].当代医学，2013,19(35):161.
• [123] 沈斌，朱国双，吴文静，等.健脾补肾活血化浊方对糖尿病肾病小鼠FGF23/Pit-1信号通路及血管钙化的影响[J].中药材，2020,43(12):3005.
• [124] 张璐芸，邓跃毅，陈万佳.健脾补肾通络方对慢性肾脏疾病患者血管钙化及微炎症状态的影响[J].中药药理与临床，2020,36(1):189.
• [125] 张旭，赵芳园.益气活血化瘀汤对慢性肾衰竭大鼠钙磷代谢紊乱及血管钙化的影响及其机制研究[J].中国现代医学杂志，2022,32(12):25.
• [126] 葛红娣，刘秀艳，翟力军.保肾汤对高通量血液透析尿毒症患者肾功能指标水平及血管钙化的影响[J].世界中西医结合杂志，2021,16(8):1491.
• [127] 王长江，王悦，王小琴，等.左归丸对5/6肾切除大鼠IL-1β、p65及胸主动脉钙化的影响[J].中国中西医结合肾病杂志，2023,24(7):573.
• [128] 黎波，龚向京，何虹材，等.右归饮对去卵巢血管钙化大鼠NMDAR1蛋白表达的影响[J].实用中西医结合临床，2015,15(12):1.
• [129] 张旭升，朱平先，黄战军，等.麝香保心丸对实验大鼠血管钙化的作用[J].中西医结合心脑血管病杂志，2015,13(1):52.
• [130] 詹理睿，王小琴，邹新蓉，等.肾元颗粒影响糖尿病小鼠肾脏中miR-199b-5p与钙磷代谢的研究[J].中华中医药学刊，2017,35(11):2819.
• [131] 王婷玉.虫草保肾颗粒对5/6肾切除大鼠钙磷代谢的影响[D].哈尔滨：黑龙江省中医药科学院，2019.
• [132] 郝媌.基于和络泄浊，培土宁风法探讨和肾络宁风颗粒对慢性肾衰竭钙磷代谢紊乱的干预机制[D].济南：山东中医药大学，2018.
• [133] XU Z,LIU X,LI Y,et al.Shuxuetong injection simultaneously ameliorates dexamethasone-driven vascular calcification and osteoporosis[J].Exp Ther Med,2021,21(3):197.