落新妇甙抑制冠心病心肌缺血再灌注损伤的保护机制研究
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摘要
目的：冠状动脉粥样硬化性心脏病(coronary heart disease, CAD),简称冠心病,是严重威胁人类健康,常导致患者猝死的常见疾病,随着冠状动脉搭桥术(coronary artery bypass graft, CABG)、溶栓疗法、体外循环、心脏移植、药物洗脱支架(drug eluting stent,DES)及经皮冠状动脉成形术(percutaneous transcoronary angioplasty, PTCA)的广泛开展,急性心肌梗死的死亡率和预后有了明显的改善,然而冠心病发作和治疗中因为缺血再灌注(Ischemia/Reperfusion, I/R)造成的心肌损伤使严重影响了冠脉血运重建后即时的生存率和远期心功能的恢复。
落新妇苷(Astilbin)是从土茯苓的乙醇提取液中分离得到的3个二氢黄酮醇甙之
具有抗炎症、抗氧化功能。我院心胸外科高思海教授2003年使用从赤土茯苓提取落新妇苷首次在离体心脏模型发现其对心肌缺血再灌注损伤有抑制作用。本研究以此为基础,进一步从细胞、器官和整体水平全面研究落新妇苷对冠心病心肌缺血再灌注损伤的保护作用机制。
方法：以Balb/c小鼠为研究对象,将小鼠随机分成4组：非缺血正常对照组(Control group,C组)、缺血再灌注阳性对照组(Ischemia reperfusion group,I组)、落新妇苷低剂量治疗组(Low dosage Astilbin treatment group, L组)和落新妇苷高剂量治疗组(High dosage Astilbin treatment group, H组),分别取其乳鼠培养心肌细胞、小鼠心脏体外灌流和小鼠冠状动脉左前降支主干(LAD)结扎心肌梗塞模型,按标准心肌缺血再灌注进行处理,分别检测心肌细胞病理改变、氧化应激水平：ROS、MDA、SOD;炎症反应：NF-κB转录活性(EMSA)、TNF-α、IL-6的mRNA和蛋白水平；心肌细胞凋亡(TUNEL)。
结果：缺血再灌注处理后出现典型心肌细胞损伤病理改变、氧化应激、炎症反应和心肌细胞凋亡。落新妇苷治疗组上述改变均有减轻及改善,有剂量依赖关系。
结论：落新妇苷能够有效减轻心肌缺血再灌注损伤,其保护作用可能与抑制心肌缺血再灌注后氧化应激、减少炎症细胞因子分泌,从而减少心肌细胞凋亡有关。说明落新妇苷有抗氧化、抗炎症作用。
Backgroud:Coronary heart disease become the first killer for adult. Myocardial ischemia and acute infarction arise secondary to atherosclerosis, followed by plaque rupture and thrombosis. Current treatments aim to terminate ischemiaby re-establishing blood flow as soon as possible. However, reperfusion may cause new damage, reperfusion injury, Several mechanisms have been proposed, such as rapid entry of sodium ions and water into myocardial cells producing intracellular edema during ischemia. Rapid entry of calcium ions produces the contraction bands and mitochondrial granules. Loss of vascular integrity results in hemorrhage into the infarct. Finally, the production of reactive oxygen species (ROS) is responsible for the peroxidation of membrane lipids and disruption of membrane integrity. Further, ischemia and reperfusion may alter the myocardial redox status and therefore the ability to detoxify ROS. Also, ROS can stimulate inflammation system,active NF-κB and produce pro inflammation cytokines such as IL-2、IL-6、TNF-α、INF-y, which can contribute to the server reperfusion damage.The drug which suppress ROS and inflammation is hopfully to prevent ischemia-reperfusion injury.
OBJECTIVE:To investigate the protective effects of astilbin on heart ischemia-reperfusion (IR) injury in mice.from-3 levels:in vitro myocardial cell culture、ex vivo langendorff heart perfusion、in vivo LAD ligation in mice.
METHODS:C57BL/6 mice were randomly allocated into 4 groups:no ischemia control group, C; Ischemia reperfusion group, I; Low dosage Astilbin treatment group,L; High dosage Astilbin treatment group, H。After ischemia reperfusion, the myocardial cells or heart from each group were studied. histological changes of the cardiac tissues were detected to evaluate injury. the level of ROS、MDA、SOD of the sample were measured by kit, TNF-a measured by RT-PCR and immunohistochemistry,NF-κB measured by EMSA.serum IL-6 level measued by ELISA, cardiac myocyte apoptosis tested by TUNEL
RESULTS:Compared with the untreated ischemia group, activities of SOD were diminished and ROS、MDA level increased obviously in IR group, whereas pretreatment with Astilbin significantly blunted the decrease of SOD activity, less ROS production and lower MDA level. and similar results were also found in histological examination. The NF-κB activity、expression of TNF-a mRNA and protein of cardial tissues in the astilbin group were lower than those in the untreated ischemia reperfusion group. The serum contents of IL-6 were decreased in the astilbin group as compared with the untreated ischemia reperfusion group (P<0.01).
CONCLUSION:It has been well known that oxidative stress and inflammation are two major mechanismsinvolved in the development of CAD ischemia reperfusion injury, Oxidative stress is represented as increased activity of oxidant enzymes and/or reduced activity of antioxidant enzymes. ROS produced by oxidant enzymes participates in the progression of myocardial ischemia reperfusion damage in two ways:one is the direct oxidation to the membrane、mitochondria、enzyme of cardiac myocytes; the other is as an intracellular second messenger to induce expression of pro inflammation cytokines(IL-6、TNF-α), which lead to Caspase cascade and cardiac myocytes apoptosis. Astilbin can ameliorate cardiac myocytes ischemia reperfusion injury by 2 ways:1 eliminate ROS、MDA and recover SOD, rebalance the redox state; 2 inhibiting the production of pro inflammation cytokines IL-6 and TNF-a, prohibite the activity of NF-KB. Astilbin is a safe and effective medicine for anti-ischemia reperfusion injury.
落新妇苷(Astilbin)是从土茯苓的乙醇提取液中分离得到的3个二氢黄酮醇甙之
具有抗炎症、抗氧化功能。我院心胸外科高思海教授2003年使用从赤土茯苓提取落新妇苷首次在离体心脏模型发现其对心肌缺血再灌注损伤有抑制作用。本研究以此为基础,进一步从细胞、器官和整体水平全面研究落新妇苷对冠心病心肌缺血再灌注损伤的保护作用机制。
方法：以Balb/c小鼠为研究对象,将小鼠随机分成4组：非缺血正常对照组(Control group,C组)、缺血再灌注阳性对照组(Ischemia reperfusion group,I组)、落新妇苷低剂量治疗组(Low dosage Astilbin treatment group, L组)和落新妇苷高剂量治疗组(High dosage Astilbin treatment group, H组),分别取其乳鼠培养心肌细胞、小鼠心脏体外灌流和小鼠冠状动脉左前降支主干(LAD)结扎心肌梗塞模型,按标准心肌缺血再灌注进行处理,分别检测心肌细胞病理改变、氧化应激水平：ROS、MDA、SOD;炎症反应：NF-κB转录活性(EMSA)、TNF-α、IL-6的mRNA和蛋白水平；心肌细胞凋亡(TUNEL)。
结果：缺血再灌注处理后出现典型心肌细胞损伤病理改变、氧化应激、炎症反应和心肌细胞凋亡。落新妇苷治疗组上述改变均有减轻及改善,有剂量依赖关系。
结论：落新妇苷能够有效减轻心肌缺血再灌注损伤,其保护作用可能与抑制心肌缺血再灌注后氧化应激、减少炎症细胞因子分泌,从而减少心肌细胞凋亡有关。说明落新妇苷有抗氧化、抗炎症作用。
Backgroud:Coronary heart disease become the first killer for adult. Myocardial ischemia and acute infarction arise secondary to atherosclerosis, followed by plaque rupture and thrombosis. Current treatments aim to terminate ischemiaby re-establishing blood flow as soon as possible. However, reperfusion may cause new damage, reperfusion injury, Several mechanisms have been proposed, such as rapid entry of sodium ions and water into myocardial cells producing intracellular edema during ischemia. Rapid entry of calcium ions produces the contraction bands and mitochondrial granules. Loss of vascular integrity results in hemorrhage into the infarct. Finally, the production of reactive oxygen species (ROS) is responsible for the peroxidation of membrane lipids and disruption of membrane integrity. Further, ischemia and reperfusion may alter the myocardial redox status and therefore the ability to detoxify ROS. Also, ROS can stimulate inflammation system,active NF-κB and produce pro inflammation cytokines such as IL-2、IL-6、TNF-α、INF-y, which can contribute to the server reperfusion damage.The drug which suppress ROS and inflammation is hopfully to prevent ischemia-reperfusion injury.
OBJECTIVE:To investigate the protective effects of astilbin on heart ischemia-reperfusion (IR) injury in mice.from-3 levels:in vitro myocardial cell culture、ex vivo langendorff heart perfusion、in vivo LAD ligation in mice.
METHODS:C57BL/6 mice were randomly allocated into 4 groups:no ischemia control group, C; Ischemia reperfusion group, I; Low dosage Astilbin treatment group,L; High dosage Astilbin treatment group, H。After ischemia reperfusion, the myocardial cells or heart from each group were studied. histological changes of the cardiac tissues were detected to evaluate injury. the level of ROS、MDA、SOD of the sample were measured by kit, TNF-a measured by RT-PCR and immunohistochemistry,NF-κB measured by EMSA.serum IL-6 level measued by ELISA, cardiac myocyte apoptosis tested by TUNEL
RESULTS:Compared with the untreated ischemia group, activities of SOD were diminished and ROS、MDA level increased obviously in IR group, whereas pretreatment with Astilbin significantly blunted the decrease of SOD activity, less ROS production and lower MDA level. and similar results were also found in histological examination. The NF-κB activity、expression of TNF-a mRNA and protein of cardial tissues in the astilbin group were lower than those in the untreated ischemia reperfusion group. The serum contents of IL-6 were decreased in the astilbin group as compared with the untreated ischemia reperfusion group (P<0.01).
CONCLUSION:It has been well known that oxidative stress and inflammation are two major mechanismsinvolved in the development of CAD ischemia reperfusion injury, Oxidative stress is represented as increased activity of oxidant enzymes and/or reduced activity of antioxidant enzymes. ROS produced by oxidant enzymes participates in the progression of myocardial ischemia reperfusion damage in two ways:one is the direct oxidation to the membrane、mitochondria、enzyme of cardiac myocytes; the other is as an intracellular second messenger to induce expression of pro inflammation cytokines(IL-6、TNF-α), which lead to Caspase cascade and cardiac myocytes apoptosis. Astilbin can ameliorate cardiac myocytes ischemia reperfusion injury by 2 ways:1 eliminate ROS、MDA and recover SOD, rebalance the redox state; 2 inhibiting the production of pro inflammation cytokines IL-6 and TNF-a, prohibite the activity of NF-KB. Astilbin is a safe and effective medicine for anti-ischemia reperfusion injury.
引文
1. Sheridan SL, Viera AJ, Krantz MJ, et al. The effect of giving global coronary risk information to adults:a systematic review. Cardiovascular Health Intervention Research and Translation Network Work Group on Global Coronary Heart Disease Risk.Arch Intern Med.2010,170(3):230-239.
2. Yavuz S.Surgery as early revascularization after acute myocardial infarction.Anadolu Kardiyol Derg.2008, Suppl 2:84-92.
3. Koca V, Ari H. Angioplasty as early revascularization in acute myocardial infarction. Anadolu Kardiyol Derg.2008,8 Suppl 2:77-83.
4. Sadat U.Signaling pathways of cardioprotective ischemic preconditioning.Int J Surg. 2009,7(6):490-498.
5. Ramachandran A, Jha S, Lefer DJ.Pthophysiology of myocardial reperfusion injury: the role of genetically engineered mouse models.Vet Pathol.2008,5(5):698-706.
6. Fischell TA. Pharmaceutical interventions for the management of no-reflow. J Invasive Cardiol.2008,20(7):374-379.
7. Schomig A, Ndrepepa G, Kastrati A.Late myocardial salvage:time to recognize its reality in the reperfusion therapy of acute myocardial infarction.Eur Heart J.2006, 27(16):1900-1907.
8. Misra MK, Sarwat M, Bhakuni P, et al. Oxidative stress and ischemic myocardial syndromes.Med Sci Monit.2009,15(10):RA209-219.
9. Burwell LS, Brookes PS. Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury. Antioxid Redox Signal.2008,10(3): 579-599.
10. Latanich CA, Toledo-Pereyra LH. Searching for NF-kappaB-based treatments of ischemia reperfusion injury. J Invest Surg.2009,22(4):301-315.
11. Zhang M, Chen L. Status of cytokines in ischemia reperfusion induced heart injury. Cardiovasc Hematol Disord Drug Targets.2008,8(3):161-172.
12.陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮醇甙的研究.中国中药杂志,1996,21(6)：355-357.
13.石明达,张朝辉,易以军等.土茯苓及其制剂中落新妇甙含量测定.时珍国药.1999,10(11)：817-818.
14.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响.中华小儿外科杂志.2006,27(2)：87-89.
15. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-alpha production and T lymphocytes adhesion. J Pharm Pharmacol. 2004,56(4):495-502.
16.高思海,潘铁成.落新妇甙的提取及对心肌缺血再灌注损伤的保护作用研究.中华实用中西医杂志.2003,3(16)：1693-1694.
17. Diaz RJ, Wilson GJ. Studying ischemic preconditioning in isolated cardiomyocyte models. Cardiovasc Res.2006,70(2):286-296.
18. Woodcock EA, Matkovich SJ. Cardiomyocytes structure, function and associated pathologies.Int J Biochem Cell Biol.2005,37(9):1746-1751.
19. White SM, Constantin PE, Claycomb WC. Cardiac physiology at the cellular level:use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function. Am J Physiol Heart Circ Physiol.2004,286(3):H823-829.
20. Kaestner L, Scholz A, Hammer K, et al. Isolation and genetic manipulation of adult cardiac myocytes for confocal imaging. J Vis Exp.2009,17(31):1433.
21. Xu X, Colecraft HM.Primary culture of adult rat heart myocytes. J Vis Exp.2009, 16(28):1308.
22.张天一,李靖,顾君一等.黄芪皂甙对培养心肌细胞缺氧复氧损伤保护作用的电镜观察.临床与实验病理学杂志.1997,12(4)：143-146.
23.吴玉兰.酸枣仁炮制品中总皂苷的抗心肌缺血作用.南京中医药大学学报(自然科学版).2004,14(3)：24.
24. Simpson, Savior S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Circ Res.1982,50:101.
25. Camelliti P, Green CR, Kohl P.Structural and functional coupling of cardiac myocytes and fibroblasts.Adv Cardiol.2006,42:132-149.
26. Milano G, von Segesser LK, Morel S, et al. Phosphorylation of phosphatidylinositol-3-kinase-protein kinase B and extracellular signal-regulated kinases 1/2 mediate reoxygenation-induced cardioprotection during hypoxia. Exp Biol Med (Maywood).2010,235(3):401-410.
27. Skrzypiec-Spring M, Grotthus B, Szelag A, et al. Isolated heart perfusion according to Langendorff—still viable in the new millennium. J Pharmacol Toxicol Methods.2007, 55(2):113-126.
28. Gao FF, Hao SY, Huang ZQ, et al. Cardiac electrophysiological and antiarrhythmic effects of N-n-butyl haloperidol iodide.Cell Physiol Biochem.2010,25(4-5):433-442.
29.宋少华,沈筱芸,刘芳.落新妇苷对大鼠肾脏缺血再灌注损伤的保护作用.中西医结合学报,2009,7(8)：132-133.
30.慕宁,王海梁,傅宏等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝
脏.第二军医大学学报,2008,29(12)：145-147.
31. Ding C, Gepstein L, Nguyen DT, et al. High-Resolution Optical Mapping of Ventricular Tachycardia in Rats with Chronic Myocardial Infarction. Pacing Clin Electrophysiol.2010,18(2):165-167.
32. Sun HY, Xue FS, Xu YC, et al. Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts.Chin Med J (Engl).2009,122(24):3048-3054.
33. Liu B, Zhu X, Chen CL, et al. Opening of the mitoKATP channel and decoupling of mitochondrial complex Ⅱ and Ⅲ contribute to the suppression of myocardial reperfusion hyperoxygenation.Mol Cell Biochem.2010,337(1-2):25-38.
34. Zhu X, Liu B, Zhou S, Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption. Am J Physiol Heart Circ Physiol.2007,293(3):H1442-50.
35.苏衍卿,王玉卿,刘秀菊.土茯苓临证古今谈.现代中西医结合杂志.2002,11(17)：1705-1706.
36.曹正中.土茯苓化学成分的研究.中草药,1993,2(11)：234.
37.周邦靖编著.常用中药的抗菌作用及其测定方法,第1版,重庆：科学技术文献出版社重庆分社,1 987：54-55.
38.黄泰康主编.常用中药成分与药理手册.第1版,北京：中国医药科技出版社,1994：206-208.
39.张克锦.赤土茯苓醋酸乙酯提取物对儿茶酚胺作用的研究.中草药,1991,22(10)：460.
40.徐强.土茯苓对细胞免疫和体液免疫的影响.中国免疫学杂志,1993,9(1)：39.
41.吴丽明.土茯苓中落新妇甙的利尿和镇痛作用.中药材,1995,18(12)：627.
42. Ennings RB, Sommers HM, Smyth GA, Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol.1960,70:68-78.
43. Fang J, Seki T, Qin H,et al. Tissue protective effect of xanthine oxidase inhibitor,
polymer conjugate of (styrene-maleic acid copolymer) and (4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine), on hepatic ischemia-reperfusion injury. Exp Biol Med (Maywood).2010,235(4):487-496.
44. Ke JJ, Yu FX, Rao Y, et al. Adenosine postconditioning protects against myocardial ischemia-reperfusion injury though modulate production of TNF-alpha and prevents activation of transcription factor NF-kappaB. Mol Biol Rep.2010,9(11):243-246.
45. Pak S, Kondo T, Nakano Y, et al. Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. Platelets.2010,11(13): 668-674.
46. Abarbanell AM, Wang Y, Herrmann JL, et al. Toll-like receptor-2 mediates mesenchymal stem cell associated myocardial recovery and VEGF production following acute ischemia/reperfusion injury. Am J Physiol Heart Circ Physiol.2010, 19(8):257-262.
47. Niemann JT, Rosborough JP, Youngquist S,Cardiac Function and the Proinflammatory Cytokine Response After Recovery From Cardiac Arrest in Swine. J Interferon Cytokine Res.2009,30(18):657-661.
48.梁日欣,廖福龙,韩东.川芎嗪预处理对清醒大鼠心肌缺血再灌注损伤的保护作用.中国实验方剂学杂志.2002,8(1)：124-125.
49.梁日欣,廖福龙,李文等,川芎嗪的药理性预适应对麻醉大鼠心肌缺血再灌注损伤的保护作用.中药药理与临床.1999,12(15)：13.
50. Thuc LC, Teshima Y, Takahashi N, et al. Mitochondrial K(ATP) channels-derived reactive oxygen species activate pro-survival pathway in pravastatin-induced cardioprotection. Apoptosis.2010,12.
51. Ghibu S, Richard C, Vergely C, et al. Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol.2009,54(5):391-398.
52. Valdivia A, Perez-Alvarez S, Aroca-Aguilar JD, et al. Superoxide dismutases:a
physiopharmacological update. J Physiol Biochem.2009,65(2):195-208.
53. Zhou L, Cortassa S, Wei AC, et al. Modeling cardiac action potential shortening driven by oxidative stress-induced mitochondrial oscillations in guinea pig cardiomyocytes. Biophys J.2009,97(7):1843-1852.
54. Misra MK, Sarwat M, Bhakuni P, et al. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit.2009,15(10):RA209-219.
55. Lamberts RR, Onderwater G, Hamdani N, et al. Reactive oxygen species-induced stimulation of 5'AMP-activated protein kinase mediates sevoflurane-induced cardioprotection.Circulation.2009,120(11 Suppl):S10-15.
56. Zhu X, Zuo L, Cardounel AJ, et al. Characterization of in vivo tissue redox status, oxygenation, and formation of reactive oxygen species in postischemic myocardium. Antioxid Redox Signal.2007,9(4):447-455.
57. Xu Y, Liu B, Zweier JL, et al. Formation of hydrogen peroxide and reduction of peroxynitrite via dismutation of superoxide at reperfusion enhances myocardial blood flow and oxygen consumption in postischemic mouse heart. J Pharmacol Exp Ther. 2008,327(2):402-410.
58. Korge P, Ping P, Weiss JN. Reactive oxygen species production in energized cardiac mitochondria during hypoxia/reoxygenation:modulation by nitric oxide. Circ Res. 2008,103(8):873-880.
59. Closa D, Torres M, Hotter G, et al. Prostanoids and free radicals in C14C-induced hepatotoxicity in rats:effect of astilbin. Prostaglandins Leukot Essent Fatty Acids. 1997,56(4):331-334.
60. Yoshiyuki Kimura, Maho Sumiyoshi, Masahiro Sakanaka. Effects of Astilbe thunbergii rhizomes onwound healing Partl. Isolation of promotional effectors from Astilbe thunbergii rhizomes on bumwound healing. J Ethnopharmacology.2007,109(1): 72-77.
61. Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm Res.2003,52(8):334-340.
62. Cai Y, Chen T, Xu Q. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol.2003,55(5):691-696.
63.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,7(10)：235-236.
64. Jiang Jianqing. Activation Change of Nuclear Nuclear Factor-KB and Influence on Adhesion ofPolymorphonuclear Neutriphils in Myocardial Ischemic-reperfusion Injury. Chin J Clin Thorac Cardiovasc Surg.2002,9(1):1450-1456.
65. Wang Yongyi, Xue Song, Xiao Mingdi, et al.bSignif icance of NF-κB activation in the rat heart ischemia2reperfusion injury. Chin J Exp Surg.2004,21(5):577-579.
66. Li C, B row der W, Kao RL. Early activation of transcription factor NF-κB during ischemia in perfusedr at heart. Am J Physiol Heart Circ Physiol.2001,280(3):H1264-1271.
67. Liu P, Xu B, Spokas E,et al. Role of endogenous nitric oxide in TNF-alpha and IL-lbeta generation in hepatic ischemia-repefusion. Shock.2000,13(3):217-223.
68. Qiang Xu, Feihua Wu, Jingsong Cao, et al. Astilbin selectively induces dysfunction of liver-infiltrating cells-novel protection from liver damage. Eur J Pharmacol.1999, 377(1):93-100.
1.苏衍卿,王玉卿,刘秀菊.土茯苓临证古今谈.现代中西医结合杂志.2002,11(17)：1705-1706.
2. 周邦靖编著.常用中药的抗菌作用及其测定方法,第1版,重庆：科学技术文献出版社重庆分社,1987：54-55.
3.黄泰康主编.常用中药成分与药理手册.第1版,北京：中国医药科技出版社,1994：206-208.
4. 张克锦.赤土茯苓醋酸乙酯提取物对儿茶酚胺作用的研究.中草药.1991,22(10)：460.
5.张克锦.赤土茯苓提取物对实验性鹌鹑脉粥样硬化的预防作用.中草药.1991,22(9)：411.
6. 徐强.土茯苓对细胞免疫和体液免疫的影响.中国免疫学杂志.1993,9(1)：39.
7.吴丽明.土茯苓中落新妇甙的利尿和镇痛作用.中药材.1995,18(12)：627.
8. 曹正中.土茯苓化学成分的研究.中草药.1993,2(11)：234.
9.石明达,张朝辉,易以军等.土茯苓及其制剂中落新妇甙含量测定时珍国药.1999,10(11)：817-818.
10.陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮醇甙的研究.中国中药杂志.1996,21(6)：355-357.
11.高思海,潘铁成.落新妇甙的提取及对心肌缺血再灌注损伤的保护作用研究.中华实用中西医杂志.2003,3(16)：1693-1694.
12.宋少华,沈筱芸,刘芳.落新妇苷对大鼠肾脏缺血再灌注损伤的保护作用.中西医结合学报.2009,7(8)：132-133.
13.慕宁,王海梁,傅宏等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏.第二军医大学学报.2008,29(12)：145-147.
14.新华·那比,艾尼瓦尔,周承明等.赤土茯苓苷对离体大鼠心脏缺血再灌注损伤的保护作用.西北药学杂志.2000,12(3)：110-111.
15. Closa D, Torres M, Hotter G, et al. Prostanoids and free radicals in C14C-induced hepatotoxicity in rats:effect of astilbin. Prostaglandins Leukot Essent Fatty Acids. 1997,56(4):331-334.
16. Haraguchi H, Mochida Y, Sakai S, et al. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis. Biosci Biotechnol Biochem.1996,60(6): 945-948.
17.陈涛,潘铁成,高思海等.落新妇甙对小鼠心脏移植排斥反应的抑制作用.山东医药.2006,46(33)：7-8.
18.林慧庆,王建军,唐建.落新妇甙对肺移植术后急性排斥反应的作用.中国胸心血管外科临床杂志.2008,15(5)：365-368.
19.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响.中华小儿外科杂志.2006,27(2)：87-89.
20.高思海,潘铁成,黄亚非等.小鼠心脏移植急性排斥反应体外模型的建立.中华实验外科杂志.2003,11(12)：256-258.
21.高思海,李平,陈涛等.落新妇苷对心脏移植排斥反应中活化T细胞p38丝裂原激活蛋白激酶信号传导通路的影响.中国医院药学杂志.2007,27(2)：153-156.
22. Song SH, Shen XY, Ding GS, et al Effects of astilbin on maturation and immunologic function of mouse bone marrow-derived dendritic cells. Zhong Xi Yi Jie He Xue Bao. 2010,8(2):145-151.
23. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-alpha production and T lymphocytes adhesion. J Pharm Pharmacol. 2004,56(4):495-502.
24. Yi HW, Lu XM, Fang F, et al Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-alpha and its associated MMP-9 activity and CD44 expression. Int Immunopharmacol.2008,8(10):1467-1474. Epub 2008 Jul 9. Erratum in:Int Immunopharmacol.2009,9(2):259.
25. Fei M, Wu X, Xu Q. Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A. J Allergy Clin Immunol.2005, 116(6):1350-1356. Epub 2005 Oct 3.
26. Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm Res.2003,52(8):334-340.
27. Cai Y, Chen T, Xu Q. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol.2003,55(5):691-696.
28. Li GS, Jiang WL, Yue XD, et al. Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro. Planta Med.2009,75(14):1470-1475. Epub 2009 Jun 16.
29.高思海,李平,陈涛等.落新妇甙对小鼠心脏移植后移植物血管病的抑制作用.中华器官移植杂志.2005,26(11)：682-683.
30. Yoshiyuki Kimura, Maho Sumiyoshi, Masahiro Sakanaka. Effects of Astilbe thunbergii rhizomes onwound healing Partl. Isolation of promotional effectors from Astilbe thunbergii rhizomes on bumwound healing. J Ethnopharmacology.2007,109(1): 72-77.
31.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,7(10)：235-236.
32. Qiang Xu, Feihua Wu, Jingsong Cao, et al. Astilbin selectively induces dysfunction of liver-infiltrating cells-novel protection from liver damage. Eur J Pharmacol.1999, 377(1):93-100.
33.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,8(10)：1336-1338.
34.高思海,李平,潘铁成等.落新妇甙诱导小鼠心脏移植体外排斥反应中活化T细胞凋亡.中华实验外科杂志.2004,21(4)：213-215.
35.高思海,李平,陈涛等.落新妇甙对心脏移植效应性T细胞磷脂酰肌醇信号通路的影响.中华胸心血管外科杂志.2007,23(1)：47-49.
36.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中活化T细胞蛋白激酶C传 导通路的影响.中华儿科杂志.2007,29(1)：35-38.
37.高思海,潘铁成,李平等.落新妇甙对同种反应性T细胞Fas、FasL、TNF-RI和TNF-R2基因表达的调控.中华实用中西医杂志.2004,4(17)：217-218.
38.陈涛,潘铁成,高思海等.落新妇甙对小鼠移植心肌细胞凋亡的抑制作用.江西医学院学报.2006,46(5)：17-18.
39.富永敏夫.药学杂言志.1960,80(10)：1340-1345；80(9)：1202-1212.
40.江苏新医学院编.中药大辞典(上册).第1版,上海：上海科学技术出版.1986：91-93.
41.多继诚.50年代391例梅毒五种方剂临床研究.内蒙古中医药.1990,9(2)：13
42.刘圣.中成药在治疗银屑病中的应用.中成药.1996,18(1)：27
43.陈文明.饮服土茯苓泡剂和外搽黄连酊治疗青年扁平疣.临床皮肤科杂志.1982,11(4)：208.
44.马英生.赤茯苓合剂灌肠治疗慢性溃疡型结肠炎50例.天津中医.1993,2(1)：36.
45.杨庆仙.赤土茯苓治疗冠心病的初步临床观察.中国新药杂志.1992,1(3)：56.
46.袁曙光.高耀风重用土茯苓治疗顽固性头痛45例观察.河北中医.1988,10(6)：4.
47.庄国康,刘瓦莉编.中药中毒与解救.第1版,北京：中国医药科技出版.1991：195-199.
48.李强.土茯苓现代研究概述.中国药业.2008,17(14)：76-78.
49.杜鹛,薛洁,周承明等.赤土茯苓对试验性胃溃疡的保护作用.中草药.2000,31(4)：277-288.
50.孙晓龙,王宽宇,张丹琦等.土茯苓注射液对大鼠血栓形成影响的实验研究.中国中医药科技.2004,11(4)：229-331.
51.杨德安,石炳毅,李炎唐等.猪芩、土茯苓和硒对膀胱化学致癌抑制作用的实验研究.中华医学杂志.1987,67(11)：67-70.
52.邱光清,许连好,林洁娜等.土茯苓总皂的抗肿瘤作用研究.中药药理与临床.2001,17(5)：39.
2. Yavuz S.Surgery as early revascularization after acute myocardial infarction.Anadolu Kardiyol Derg.2008, Suppl 2:84-92.
3. Koca V, Ari H. Angioplasty as early revascularization in acute myocardial infarction. Anadolu Kardiyol Derg.2008,8 Suppl 2:77-83.
4. Sadat U.Signaling pathways of cardioprotective ischemic preconditioning.Int J Surg. 2009,7(6):490-498.
5. Ramachandran A, Jha S, Lefer DJ.Pthophysiology of myocardial reperfusion injury: the role of genetically engineered mouse models.Vet Pathol.2008,5(5):698-706.
6. Fischell TA. Pharmaceutical interventions for the management of no-reflow. J Invasive Cardiol.2008,20(7):374-379.
7. Schomig A, Ndrepepa G, Kastrati A.Late myocardial salvage:time to recognize its reality in the reperfusion therapy of acute myocardial infarction.Eur Heart J.2006, 27(16):1900-1907.
8. Misra MK, Sarwat M, Bhakuni P, et al. Oxidative stress and ischemic myocardial syndromes.Med Sci Monit.2009,15(10):RA209-219.
9. Burwell LS, Brookes PS. Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury. Antioxid Redox Signal.2008,10(3): 579-599.
10. Latanich CA, Toledo-Pereyra LH. Searching for NF-kappaB-based treatments of ischemia reperfusion injury. J Invest Surg.2009,22(4):301-315.
11. Zhang M, Chen L. Status of cytokines in ischemia reperfusion induced heart injury. Cardiovasc Hematol Disord Drug Targets.2008,8(3):161-172.
12.陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮醇甙的研究.中国中药杂志,1996,21(6)：355-357.
13.石明达,张朝辉,易以军等.土茯苓及其制剂中落新妇甙含量测定.时珍国药.1999,10(11)：817-818.
14.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响.中华小儿外科杂志.2006,27(2)：87-89.
15. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-alpha production and T lymphocytes adhesion. J Pharm Pharmacol. 2004,56(4):495-502.
16.高思海,潘铁成.落新妇甙的提取及对心肌缺血再灌注损伤的保护作用研究.中华实用中西医杂志.2003,3(16)：1693-1694.
17. Diaz RJ, Wilson GJ. Studying ischemic preconditioning in isolated cardiomyocyte models. Cardiovasc Res.2006,70(2):286-296.
18. Woodcock EA, Matkovich SJ. Cardiomyocytes structure, function and associated pathologies.Int J Biochem Cell Biol.2005,37(9):1746-1751.
19. White SM, Constantin PE, Claycomb WC. Cardiac physiology at the cellular level:use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function. Am J Physiol Heart Circ Physiol.2004,286(3):H823-829.
20. Kaestner L, Scholz A, Hammer K, et al. Isolation and genetic manipulation of adult cardiac myocytes for confocal imaging. J Vis Exp.2009,17(31):1433.
21. Xu X, Colecraft HM.Primary culture of adult rat heart myocytes. J Vis Exp.2009, 16(28):1308.
22.张天一,李靖,顾君一等.黄芪皂甙对培养心肌细胞缺氧复氧损伤保护作用的电镜观察.临床与实验病理学杂志.1997,12(4)：143-146.
23.吴玉兰.酸枣仁炮制品中总皂苷的抗心肌缺血作用.南京中医药大学学报(自然科学版).2004,14(3)：24.
24. Simpson, Savior S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Circ Res.1982,50:101.
25. Camelliti P, Green CR, Kohl P.Structural and functional coupling of cardiac myocytes and fibroblasts.Adv Cardiol.2006,42:132-149.
26. Milano G, von Segesser LK, Morel S, et al. Phosphorylation of phosphatidylinositol-3-kinase-protein kinase B and extracellular signal-regulated kinases 1/2 mediate reoxygenation-induced cardioprotection during hypoxia. Exp Biol Med (Maywood).2010,235(3):401-410.
27. Skrzypiec-Spring M, Grotthus B, Szelag A, et al. Isolated heart perfusion according to Langendorff—still viable in the new millennium. J Pharmacol Toxicol Methods.2007, 55(2):113-126.
28. Gao FF, Hao SY, Huang ZQ, et al. Cardiac electrophysiological and antiarrhythmic effects of N-n-butyl haloperidol iodide.Cell Physiol Biochem.2010,25(4-5):433-442.
29.宋少华,沈筱芸,刘芳.落新妇苷对大鼠肾脏缺血再灌注损伤的保护作用.中西医结合学报,2009,7(8)：132-133.
30.慕宁,王海梁,傅宏等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝
脏.第二军医大学学报,2008,29(12)：145-147.
31. Ding C, Gepstein L, Nguyen DT, et al. High-Resolution Optical Mapping of Ventricular Tachycardia in Rats with Chronic Myocardial Infarction. Pacing Clin Electrophysiol.2010,18(2):165-167.
32. Sun HY, Xue FS, Xu YC, et al. Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts.Chin Med J (Engl).2009,122(24):3048-3054.
33. Liu B, Zhu X, Chen CL, et al. Opening of the mitoKATP channel and decoupling of mitochondrial complex Ⅱ and Ⅲ contribute to the suppression of myocardial reperfusion hyperoxygenation.Mol Cell Biochem.2010,337(1-2):25-38.
34. Zhu X, Liu B, Zhou S, Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption. Am J Physiol Heart Circ Physiol.2007,293(3):H1442-50.
35.苏衍卿,王玉卿,刘秀菊.土茯苓临证古今谈.现代中西医结合杂志.2002,11(17)：1705-1706.
36.曹正中.土茯苓化学成分的研究.中草药,1993,2(11)：234.
37.周邦靖编著.常用中药的抗菌作用及其测定方法,第1版,重庆：科学技术文献出版社重庆分社,1 987：54-55.
38.黄泰康主编.常用中药成分与药理手册.第1版,北京：中国医药科技出版社,1994：206-208.
39.张克锦.赤土茯苓醋酸乙酯提取物对儿茶酚胺作用的研究.中草药,1991,22(10)：460.
40.徐强.土茯苓对细胞免疫和体液免疫的影响.中国免疫学杂志,1993,9(1)：39.
41.吴丽明.土茯苓中落新妇甙的利尿和镇痛作用.中药材,1995,18(12)：627.
42. Ennings RB, Sommers HM, Smyth GA, Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol.1960,70:68-78.
43. Fang J, Seki T, Qin H,et al. Tissue protective effect of xanthine oxidase inhibitor,
polymer conjugate of (styrene-maleic acid copolymer) and (4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine), on hepatic ischemia-reperfusion injury. Exp Biol Med (Maywood).2010,235(4):487-496.
44. Ke JJ, Yu FX, Rao Y, et al. Adenosine postconditioning protects against myocardial ischemia-reperfusion injury though modulate production of TNF-alpha and prevents activation of transcription factor NF-kappaB. Mol Biol Rep.2010,9(11):243-246.
45. Pak S, Kondo T, Nakano Y, et al. Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. Platelets.2010,11(13): 668-674.
46. Abarbanell AM, Wang Y, Herrmann JL, et al. Toll-like receptor-2 mediates mesenchymal stem cell associated myocardial recovery and VEGF production following acute ischemia/reperfusion injury. Am J Physiol Heart Circ Physiol.2010, 19(8):257-262.
47. Niemann JT, Rosborough JP, Youngquist S,Cardiac Function and the Proinflammatory Cytokine Response After Recovery From Cardiac Arrest in Swine. J Interferon Cytokine Res.2009,30(18):657-661.
48.梁日欣,廖福龙,韩东.川芎嗪预处理对清醒大鼠心肌缺血再灌注损伤的保护作用.中国实验方剂学杂志.2002,8(1)：124-125.
49.梁日欣,廖福龙,李文等,川芎嗪的药理性预适应对麻醉大鼠心肌缺血再灌注损伤的保护作用.中药药理与临床.1999,12(15)：13.
50. Thuc LC, Teshima Y, Takahashi N, et al. Mitochondrial K(ATP) channels-derived reactive oxygen species activate pro-survival pathway in pravastatin-induced cardioprotection. Apoptosis.2010,12.
51. Ghibu S, Richard C, Vergely C, et al. Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol.2009,54(5):391-398.
52. Valdivia A, Perez-Alvarez S, Aroca-Aguilar JD, et al. Superoxide dismutases:a
physiopharmacological update. J Physiol Biochem.2009,65(2):195-208.
53. Zhou L, Cortassa S, Wei AC, et al. Modeling cardiac action potential shortening driven by oxidative stress-induced mitochondrial oscillations in guinea pig cardiomyocytes. Biophys J.2009,97(7):1843-1852.
54. Misra MK, Sarwat M, Bhakuni P, et al. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit.2009,15(10):RA209-219.
55. Lamberts RR, Onderwater G, Hamdani N, et al. Reactive oxygen species-induced stimulation of 5'AMP-activated protein kinase mediates sevoflurane-induced cardioprotection.Circulation.2009,120(11 Suppl):S10-15.
56. Zhu X, Zuo L, Cardounel AJ, et al. Characterization of in vivo tissue redox status, oxygenation, and formation of reactive oxygen species in postischemic myocardium. Antioxid Redox Signal.2007,9(4):447-455.
57. Xu Y, Liu B, Zweier JL, et al. Formation of hydrogen peroxide and reduction of peroxynitrite via dismutation of superoxide at reperfusion enhances myocardial blood flow and oxygen consumption in postischemic mouse heart. J Pharmacol Exp Ther. 2008,327(2):402-410.
58. Korge P, Ping P, Weiss JN. Reactive oxygen species production in energized cardiac mitochondria during hypoxia/reoxygenation:modulation by nitric oxide. Circ Res. 2008,103(8):873-880.
59. Closa D, Torres M, Hotter G, et al. Prostanoids and free radicals in C14C-induced hepatotoxicity in rats:effect of astilbin. Prostaglandins Leukot Essent Fatty Acids. 1997,56(4):331-334.
60. Yoshiyuki Kimura, Maho Sumiyoshi, Masahiro Sakanaka. Effects of Astilbe thunbergii rhizomes onwound healing Partl. Isolation of promotional effectors from Astilbe thunbergii rhizomes on bumwound healing. J Ethnopharmacology.2007,109(1): 72-77.
61. Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm Res.2003,52(8):334-340.
62. Cai Y, Chen T, Xu Q. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol.2003,55(5):691-696.
63.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,7(10)：235-236.
64. Jiang Jianqing. Activation Change of Nuclear Nuclear Factor-KB and Influence on Adhesion ofPolymorphonuclear Neutriphils in Myocardial Ischemic-reperfusion Injury. Chin J Clin Thorac Cardiovasc Surg.2002,9(1):1450-1456.
65. Wang Yongyi, Xue Song, Xiao Mingdi, et al.bSignif icance of NF-κB activation in the rat heart ischemia2reperfusion injury. Chin J Exp Surg.2004,21(5):577-579.
66. Li C, B row der W, Kao RL. Early activation of transcription factor NF-κB during ischemia in perfusedr at heart. Am J Physiol Heart Circ Physiol.2001,280(3):H1264-1271.
67. Liu P, Xu B, Spokas E,et al. Role of endogenous nitric oxide in TNF-alpha and IL-lbeta generation in hepatic ischemia-repefusion. Shock.2000,13(3):217-223.
68. Qiang Xu, Feihua Wu, Jingsong Cao, et al. Astilbin selectively induces dysfunction of liver-infiltrating cells-novel protection from liver damage. Eur J Pharmacol.1999, 377(1):93-100.
1.苏衍卿,王玉卿,刘秀菊.土茯苓临证古今谈.现代中西医结合杂志.2002,11(17)：1705-1706.
2. 周邦靖编著.常用中药的抗菌作用及其测定方法,第1版,重庆：科学技术文献出版社重庆分社,1987：54-55.
3.黄泰康主编.常用中药成分与药理手册.第1版,北京：中国医药科技出版社,1994：206-208.
4. 张克锦.赤土茯苓醋酸乙酯提取物对儿茶酚胺作用的研究.中草药.1991,22(10)：460.
5.张克锦.赤土茯苓提取物对实验性鹌鹑脉粥样硬化的预防作用.中草药.1991,22(9)：411.
6. 徐强.土茯苓对细胞免疫和体液免疫的影响.中国免疫学杂志.1993,9(1)：39.
7.吴丽明.土茯苓中落新妇甙的利尿和镇痛作用.中药材.1995,18(12)：627.
8. 曹正中.土茯苓化学成分的研究.中草药.1993,2(11)：234.
9.石明达,张朝辉,易以军等.土茯苓及其制剂中落新妇甙含量测定时珍国药.1999,10(11)：817-818.
10.陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮醇甙的研究.中国中药杂志.1996,21(6)：355-357.
11.高思海,潘铁成.落新妇甙的提取及对心肌缺血再灌注损伤的保护作用研究.中华实用中西医杂志.2003,3(16)：1693-1694.
12.宋少华,沈筱芸,刘芳.落新妇苷对大鼠肾脏缺血再灌注损伤的保护作用.中西医结合学报.2009,7(8)：132-133.
13.慕宁,王海梁,傅宏等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏.第二军医大学学报.2008,29(12)：145-147.
14.新华·那比,艾尼瓦尔,周承明等.赤土茯苓苷对离体大鼠心脏缺血再灌注损伤的保护作用.西北药学杂志.2000,12(3)：110-111.
15. Closa D, Torres M, Hotter G, et al. Prostanoids and free radicals in C14C-induced hepatotoxicity in rats:effect of astilbin. Prostaglandins Leukot Essent Fatty Acids. 1997,56(4):331-334.
16. Haraguchi H, Mochida Y, Sakai S, et al. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis. Biosci Biotechnol Biochem.1996,60(6): 945-948.
17.陈涛,潘铁成,高思海等.落新妇甙对小鼠心脏移植排斥反应的抑制作用.山东医药.2006,46(33)：7-8.
18.林慧庆,王建军,唐建.落新妇甙对肺移植术后急性排斥反应的作用.中国胸心血管外科临床杂志.2008,15(5)：365-368.
19.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响.中华小儿外科杂志.2006,27(2)：87-89.
20.高思海,潘铁成,黄亚非等.小鼠心脏移植急性排斥反应体外模型的建立.中华实验外科杂志.2003,11(12)：256-258.
21.高思海,李平,陈涛等.落新妇苷对心脏移植排斥反应中活化T细胞p38丝裂原激活蛋白激酶信号传导通路的影响.中国医院药学杂志.2007,27(2)：153-156.
22. Song SH, Shen XY, Ding GS, et al Effects of astilbin on maturation and immunologic function of mouse bone marrow-derived dendritic cells. Zhong Xi Yi Jie He Xue Bao. 2010,8(2):145-151.
23. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-alpha production and T lymphocytes adhesion. J Pharm Pharmacol. 2004,56(4):495-502.
24. Yi HW, Lu XM, Fang F, et al Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-alpha and its associated MMP-9 activity and CD44 expression. Int Immunopharmacol.2008,8(10):1467-1474. Epub 2008 Jul 9. Erratum in:Int Immunopharmacol.2009,9(2):259.
25. Fei M, Wu X, Xu Q. Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A. J Allergy Clin Immunol.2005, 116(6):1350-1356. Epub 2005 Oct 3.
26. Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm Res.2003,52(8):334-340.
27. Cai Y, Chen T, Xu Q. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol.2003,55(5):691-696.
28. Li GS, Jiang WL, Yue XD, et al. Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro. Planta Med.2009,75(14):1470-1475. Epub 2009 Jun 16.
29.高思海,李平,陈涛等.落新妇甙对小鼠心脏移植后移植物血管病的抑制作用.中华器官移植杂志.2005,26(11)：682-683.
30. Yoshiyuki Kimura, Maho Sumiyoshi, Masahiro Sakanaka. Effects of Astilbe thunbergii rhizomes onwound healing Partl. Isolation of promotional effectors from Astilbe thunbergii rhizomes on bumwound healing. J Ethnopharmacology.2007,109(1): 72-77.
31.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,7(10)：235-236.
32. Qiang Xu, Feihua Wu, Jingsong Cao, et al. Astilbin selectively induces dysfunction of liver-infiltrating cells-novel protection from liver damage. Eur J Pharmacol.1999, 377(1):93-100.
33.高思海,陈涛,潘铁成等.落新妇甙对心脏移植排斥反应中活化T细胞穿孔素和颗粒酶B表达的影响.中国医师杂志.2006,8(10)：1336-1338.
34.高思海,李平,潘铁成等.落新妇甙诱导小鼠心脏移植体外排斥反应中活化T细胞凋亡.中华实验外科杂志.2004,21(4)：213-215.
35.高思海,李平,陈涛等.落新妇甙对心脏移植效应性T细胞磷脂酰肌醇信号通路的影响.中华胸心血管外科杂志.2007,23(1)：47-49.
36.高思海,李平,陈涛等.落新妇甙对心脏移植排斥反应中活化T细胞蛋白激酶C传 导通路的影响.中华儿科杂志.2007,29(1)：35-38.
37.高思海,潘铁成,李平等.落新妇甙对同种反应性T细胞Fas、FasL、TNF-RI和TNF-R2基因表达的调控.中华实用中西医杂志.2004,4(17)：217-218.
38.陈涛,潘铁成,高思海等.落新妇甙对小鼠移植心肌细胞凋亡的抑制作用.江西医学院学报.2006,46(5)：17-18.
39.富永敏夫.药学杂言志.1960,80(10)：1340-1345；80(9)：1202-1212.
40.江苏新医学院编.中药大辞典(上册).第1版,上海：上海科学技术出版.1986：91-93.
41.多继诚.50年代391例梅毒五种方剂临床研究.内蒙古中医药.1990,9(2)：13
42.刘圣.中成药在治疗银屑病中的应用.中成药.1996,18(1)：27
43.陈文明.饮服土茯苓泡剂和外搽黄连酊治疗青年扁平疣.临床皮肤科杂志.1982,11(4)：208.
44.马英生.赤茯苓合剂灌肠治疗慢性溃疡型结肠炎50例.天津中医.1993,2(1)：36.
45.杨庆仙.赤土茯苓治疗冠心病的初步临床观察.中国新药杂志.1992,1(3)：56.
46.袁曙光.高耀风重用土茯苓治疗顽固性头痛45例观察.河北中医.1988,10(6)：4.
47.庄国康,刘瓦莉编.中药中毒与解救.第1版,北京：中国医药科技出版.1991：195-199.
48.李强.土茯苓现代研究概述.中国药业.2008,17(14)：76-78.
49.杜鹛,薛洁,周承明等.赤土茯苓对试验性胃溃疡的保护作用.中草药.2000,31(4)：277-288.
50.孙晓龙,王宽宇,张丹琦等.土茯苓注射液对大鼠血栓形成影响的实验研究.中国中医药科技.2004,11(4)：229-331.
51.杨德安,石炳毅,李炎唐等.猪芩、土茯苓和硒对膀胱化学致癌抑制作用的实验研究.中华医学杂志.1987,67(11)：67-70.
52.邱光清,许连好,林洁娜等.土茯苓总皂的抗肿瘤作用研究.中药药理与临床.2001,17(5)：39.