口服槲皮素对兔耳增生性瘢痕的抑制作用
|
摘要
研究背景：体外实验提示,槲皮素具有抑制瘢痕增生的作用。但至今尚无口服槲皮素抑制瘢痕的体内实验。
研究目的：探索口服槲皮素对兔耳增生性瘢痕的抑制作用。
研究方法：在9只新西兰白兔的耳朵上建立标准创面(每耳4个,共72个)。3只白兔每天用100mg槲皮素灌胃,3只白兔每天用36mg积雪苷灌胃(阳性对照),另3只白兔不做灌胃处理(阴性对照)。4周后收集标本,从瘢痕横截面最高点制作切片,用瘢痕面积和未受创伤的基线面积之比作为瘢痕增生指数。
结果：对照组的瘢痕增生指数为1.67±0.02,积雪苷组为1.55±0.03,积雪苷组的瘢痕增生程度比对照组减少17.9%,有统计学显著性差异(p=0.003)；槲皮素组的瘢痕增生指数为1.59±0.03,瘢痕增生程度比对照组减少11.9%,但无统计学显著性差异(p=0.053)。
结论：口服积雪苷可显著抑制兔耳模型瘢痕增生,口服槲皮素对增生性瘢痕的抑制作用尚待进一步实验证实。
Background:In vitro observations suggested that quercetin had a potential for the treatment of excessive scars. There has been no study about the effect of oral quercetin on hypertrophic scarring.
Objective:to examine the effect of oral quercetin on hypertrophic scarring in the rabbit ear model.
Methods:Standardized wounds, four per ear, were created on the ears of nine New Zealand White rabbits, for a total of72scars. Three of the rabbits received daily ingestion of quercetin or asiaticoside, respectively. And the other three received no intervention. After4weeks, the resulting ear scars were harvested. Histological slides were prepared from the thickest cross-sections of the scars, and hypertrophic index was calculated by comparing the area of the scar to the baseline value of unwounded skin.
Results:Among the rabbits treated with asiaticoside, the mean hypertrophic index was1.55±0.03, compared with1.67±0.02in the control group (p=0.003), representing a17.9%reduction in hypertrophic area. Among the rabbits treated with quercetin, the mean hypertrophic index was1.59±0.03, representing a11.9%reduction in hypertrophic area, but there's no significant reduction in scar hypertrophy compared with the control group (p=0.053).
Conclusions:Orally administered asiaticoside significantly reduces the severity of hypertrophic scarring in the rabbit ear model. The inhibitory effect of oral quercetin on hypertrophic scarring still needs further investigation.
研究目的：探索口服槲皮素对兔耳增生性瘢痕的抑制作用。
研究方法：在9只新西兰白兔的耳朵上建立标准创面(每耳4个,共72个)。3只白兔每天用100mg槲皮素灌胃,3只白兔每天用36mg积雪苷灌胃(阳性对照),另3只白兔不做灌胃处理(阴性对照)。4周后收集标本,从瘢痕横截面最高点制作切片,用瘢痕面积和未受创伤的基线面积之比作为瘢痕增生指数。
结果：对照组的瘢痕增生指数为1.67±0.02,积雪苷组为1.55±0.03,积雪苷组的瘢痕增生程度比对照组减少17.9%,有统计学显著性差异(p=0.003)；槲皮素组的瘢痕增生指数为1.59±0.03,瘢痕增生程度比对照组减少11.9%,但无统计学显著性差异(p=0.053)。
结论：口服积雪苷可显著抑制兔耳模型瘢痕增生,口服槲皮素对增生性瘢痕的抑制作用尚待进一步实验证实。
Background:In vitro observations suggested that quercetin had a potential for the treatment of excessive scars. There has been no study about the effect of oral quercetin on hypertrophic scarring.
Objective:to examine the effect of oral quercetin on hypertrophic scarring in the rabbit ear model.
Methods:Standardized wounds, four per ear, were created on the ears of nine New Zealand White rabbits, for a total of72scars. Three of the rabbits received daily ingestion of quercetin or asiaticoside, respectively. And the other three received no intervention. After4weeks, the resulting ear scars were harvested. Histological slides were prepared from the thickest cross-sections of the scars, and hypertrophic index was calculated by comparing the area of the scar to the baseline value of unwounded skin.
Results:Among the rabbits treated with asiaticoside, the mean hypertrophic index was1.55±0.03, compared with1.67±0.02in the control group (p=0.003), representing a17.9%reduction in hypertrophic area. Among the rabbits treated with quercetin, the mean hypertrophic index was1.59±0.03, representing a11.9%reduction in hypertrophic area, but there's no significant reduction in scar hypertrophy compared with the control group (p=0.053).
Conclusions:Orally administered asiaticoside significantly reduces the severity of hypertrophic scarring in the rabbit ear model. The inhibitory effect of oral quercetin on hypertrophic scarring still needs further investigation.
引文
1. Sampson L, Rimm E, Hollman PC, et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc 2002; 102(10):1414-20.
2. Johannot L, Somerset SM. Age-related variations in flavonoid intake and sources in the Australian population. Public Health Nutr 2006; 9(8):1045-54.
3. Bischoff SC. Quercetin:potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008;11(6):733-40.
4. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype:a double-blinded, placebo-controlled cross-over study. Br J Nutr 2009:1-10.
5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137(11):2405-11.
6. Theoharides TC, Bielory L. Mast cells and mast cell mediators as targets of dietary supplements. Ann Allergy Asthma Immunol 2004; 93(2 Suppl 1):S24-34.
7. Hollman PC, van Trijp JM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997; 418(1-2):152-6.
8. Murota K, Shimizu S, Chujo H, et al. Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2. Arch Biochem Biophys 2000; 384(2):391-7.
9. Graf BA, Ameho C, Dolnikowski GG, et al. Rat gastrointestinal tissues metabolize quercetin. J Nutr 2006; 136(1):39-44.
10. Murota K, Terao J. Quercetin appears in the lymph of unanesthetized rats as its phase Ⅱ metabolites after administered into the stomach. FEBS Lett 2005; 579(24):5343-6.
11. Oliveira EJ, Watson DG. In vitro glucuronidation of kaempferol and quercetin by human UGT-1A9 microsomes. FEBS Lett 2000; 471(1):1-6.
12. Boersma MG, van der Woude H, Bogaards J, et al. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chem Res Toxicol 2002; 15(5):662-70.
13. Olthof MR, Hollman PC, Buijsman MN, et al. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 2003; 133(6):1806-14.
14. Chen X, Yin OQ, Zuo Z, Chow MS. Pharmacokinetics and modeling of quercetin and metabolites. Pharm Res 2005; 22(6):892-901.
15. Walle T, Walle UK, Halushka PV. Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 2001; 131(10):2648-52.
16. Egert S, Wolffram S, Bosy-Westphal A, et al. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr 2008; 138(9):1615-21.
17. de Boer VC, Dihal AA, van der Woude H, et al. Tissue distribution of quercetin in rats and pigs. J Nutr 2005; 135(7):1718-25.
18. Wang L, Morris ME. Liquid chromatography-tandem mass spectroscopy assay for quercetin and conjugated quercetin metabolites in human plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 821(2):194-201.
19. Cross HJ, Tilby M, Chipman JK, et al. Effect of quercetin on the genotoxic potential of cisplatin. Int J Cancer 1996; 66(3):404-8.
20. Bjeldanes LF, Chang GW. Mutagenic activity of quercetin and related compounds. Science 1977; 197(4303):577-8.
21. Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med 2005; 16(2):275-8.
22. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category Ⅲ chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999; 54(6):960-3.
23. Lozoya X, Reyes-Morales H, Chavez-Soto MA, et al. Intestinal anti-spasmodic effect of a phytodrug of Psidium guajava folia in the treatment of acute diarrheic disease. J Ethnopharmacol 2002;83(1-2):19-24.
24. Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996; 2(4):659-68.
25. Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food ChemToxicol 2007; 45(11):2179-205.
26. Boots AW, Haenen GR, Bast A. Health effects of quercetin:from antioxidant to nutraceutical. Eur J Pharmacol 2008; 585(2-3):325-37.
27. Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 1994; 16(6):845-50.
28. Haenen GR, Bast A. Nitric oxide radical scavenging of flavonoids. Methods Enzymol 1999; 301:490-503.
29. Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 1997; 236(3):591-3.
30. Loke WM, Proudfoot JM, McKinley AJ, et al. Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 2008; 56(10):3609-15.
31. Shutenko Z, Henry Y, Pinard E, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 1999; 57(2):199-208.
32. Huk I, Brovkovych V, Nanobash Vili J, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury:an experimental study. Br J Surg 1998; 85(8):1080-5.
33. Zhu JX, Wang Y, Kong LD, et al. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004; 93(1):133-40.
34. Bindoli A, Valente M, Cavallini L. Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity. Pharmacol Res Commun 1985; 17(9):831-9.
35. Emura K, Yokomizo A, Toyoshi T, Moriwaki M. Effect of enzymatically modified isoquercitrin in spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 2007; 53(1):68-74.
36. Jalili T, Carlstrom J, Kim S, et al. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 2006; 47(4):531-41.
37. Duarte J, Jimenez R, O'Valle F, et al. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 2002; 20(9):1843-54.
38. Perez-Vizcaino F, Duarte J, Jimenez R, et al. Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 2009; 61(1):67-75.
39. Rivera L, Moron R, Sanchez M, et al. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring) 2008; 16(9):2081-7.
40. Ahn J, Lee H, Kim S, et al. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 2008; 373(4):545-9.
41. Sheu JR, Hsiao G, Chou PH, et al. Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets. J Agric Food Chem 2004; 52(14):4414-8.
42. Hubbard GP, Stevens JM, Cicmil M, et al. Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J Thromb Haemost 2003; 1(5):1079-88.
43. Pignatelli P, Di Santo S, Carnevale R, Violi F. The polyphenols quercetin and catechin synergize in inhibiting platelet CD40L expression. Thromb Haemost 2005; 94(4):888-9.
44. Fan PS, Gu ZL, Liang ZQ. Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro. Acta Pharmacol Sin 2001; 22(9):857-60.
45. Ko WC, Wang HL, Lei CB, et al. Mechanisms of relaxant action of 3-O-methylquercetin in isolated guinea pig trachea. Planta Med 2002; 68(1):30-5.
46. Dell'Agli M, Maschi O, Galli GV, et al. Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr 2008; 99(5):945-51.
47. Pearce FL, Befus AD, Bienenstock J. Mucosal mast cells. Ⅲ. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol 1984; 73(6):819-23.
48. Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 2000;30(4):501-8.
49. Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation. J Biol Regul Homeost Agents 2006; 20(3-4):47-52.
50. Kempuraj D, Castellani ML, Petrarca C, et al. Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Clin Exp Med 2006; 6(4):150-6.
51. Bureau G, Longpre F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res 2008; 86(2):403-10.
52. Kumazawa Y, Kawaguchi K, Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha. Curr Pharm Des 2006; 12(32):4271-9.
53. Lee KW, Kang NJ, Heo YS, et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine. Cancer Res 2008; 68(3):946-55.
54. Hamalainen M, Nieminen R, Vuorela P, et al. Anti-inflammatory effects of flavonoids:genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm 2007; 2007:45673.
55. Hirpara KV, Aggarwal P, Mukherjee AJ, et al. Quercetin and its derivatives:synthesis, pharmacological uses with special emphasis on anti-tumor properties and prodrug with enhanced bio-availability. Anticancer Agents Med Chem 2009; 9(2):138-61.
56. Wong SP, Li J, Shen P, et al. Ultrasensitive cell-based bioassay for the measurement of global estrogenic activity of flavonoid mixtures revealing additive, restrictive, and enhanced actions in binary and higher order combinations. Assay Drug Dev Technol 2007; 5(3):355-62.
57. van der Woude H, Ter Veld MG, Jacobs N, et al. The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol Nutr Food Res 2005; 49(8):763-71.
58. Schlachterman A, Valle F, Wall KM, et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol 2008;1(1):19-27.
59. Yamashita N, Kawanishi S. Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin. Free Radic Res 2000; 33(5):623-33.
60. Cantero G, Campanella C, Mateos S, Cortes F. Topoisomerase Ⅱ inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin. Mutagenesis 2006; 21(5):321-5.
61. Aherne SA, O'Brien NM. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000; 29(6):507-14.
62. Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett 2008; 269(2):315-25.
63. Psahoulia FH, Drosopoulos KG, Doubravska L, et al. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther 2007; 6(9):2591-9.
64. Chen W, Wang X, Zhuang J, et al. Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells. Carcinogenesis 2007; 28(10):2114-21.
65. Kim YH, Lee YJ. TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation. J Cell Biochem 2007; 100(4):998-1009.
66. Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005; 280(7):5636-45.
67. Xing N, Chen Y, Mitchell SH, Young CY. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis 2001; 22(3):409-14.
68. Morris JD, Pramanik R, Zhang X, et al. Selenium-or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity. Cancer Lett 2006; 239(1):111-22.
69. Phan TT, Sun L, Bay BH, et al. Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro:therapeutic implication for excessive scarring. J Trauma 2003; 54(6):1212-24.
70. Phan TT, See P, Tran E, et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin:its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol 2003; 148(3):544-52.
71. Phan TT, Lim IJ, Sun L, et al. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci 2003; 33(3):192-4.
72. Phan TT, Lim IJ, Chan SY, et al. Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin:implications for the treatment of excessive scars. J Trauma 2004; 57(5):1032-7.
73. Long X, Zeng X, Zhang FQ, Wang XJ. Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts. Chin Med Sci J 2006; 21(3):179-83.
74. Saulis AS, Mogford JH, Mustoe TA. Effect of Mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002; 110(1):177-83; discussion 184-6.
75. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars:prospective double-blinded study. Dermatol Surg 2006; 32(2):193-7.
76. Cushnie TP, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents 2005; 26(5):343-56.
77. Spedding G, Ratty A, Middleton E, Jr. Inhibition of reverse transcriptases by flavonoids. Antiviral Res 1989;12(2):99-110.
78. Davis JM, Murphy EA, McClellan JL, et al. Quercetin reduces susceptibility to influenza infection following stressful exercise. Am J Physiol Regul Integr Comp Physiol 2008; 295(2):R505-9.
79. Plaper A, Golob M, Hafner I, et al. Characterization of quercetin binding site on DNA gyrase. Biochem Biophys Res Commun 2003; 306(2):530-6.
80. Gonzalez-Segovia R, Quintanar JL, Salinas E, et al. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol 2008; 43(6):441-7.
81. Lines TC, Ono M. FRS 1000, an extract of red onion peel, strongly inhibits phosphodiesterase 5 A (PDE 5A). Phytomedicine 2006; 13(4):236-9.
82. Xin ZC, Kim EK, Lin CS, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl 2003; 5(1):15-8.
83. Wang H, Liu Y, Huai Q, et al. Multiple conformations of phosphodiesterase-5:implications for enzyme function and drug development. J Biol Chem 2006; 281(30):21469-79.
84. Hu HL, Forsey RJ, Blades TJ, et al. Antioxidants may contribute in the fight against ageing:an in vitro model. Mech Ageing Dev 2000; 121(1-3):217-30.
85. Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic Res 2006; 40(10):1054-65.
86. Chopra M, Fitzsimons PE, Strain JJ, et al. Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations. Clin Chem 2000; 46(8 Pt 1):1162-70.
87. Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost 2004; 2(12):2138-45.
88. Hubbard GP, Wolffram S, de Vos R, et al. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man:a pilot study. Br J Nutr 2006; 96(3):482-8.
89. Mardla V, Kobzar G, Samel N. Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin. Platelets 2004; 15(5):319-24.
90. Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol 2001; 7(1):44-6.
91. Cermak R, Vujicic Z, Kuhn G, Wolffram S. The secretory response of the rat colon to the flavonol quercetin is dependent on Ca2+-calmodulin. Exp Physiol 2000; 85(3):255-61.
92. Cermak R, Follmer U, Wolffram S. Dietary flavonol quercetin induces chloride secretion in rat colon. Am J Physiol 1998; 275(5 Pt 1):G1166-72.
93. Kim H, Kong H, Choi B, et al. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease. Pharm Res 2005; 22(9):1499-509.
94. Rao CV, Vijayakumar M. Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin, on experimental reflux oesophagitis in rats. Eur J Pharmacol 2008; 589(l-3):233-8.
95. Boots AW, Drent M, Swennen EL, et al. Antioxidant status associated with inflammation in sarcoidosis:a potential role for antioxidants. Respir Med 2009; 103(3):364-72.
96. Hirvonen T, Virtamo J, Korhonen P, et al. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control 2001;12(9):789-96.
97. Gates MA, Tworoger SS, Hecht JL, et al. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer 2007; 121(10):2225-32.
98. Nothlings U, Murphy SP, Wilkens LR, et al. Flavonols and pancreatic cancer risk:the multiethnic cohort study. Am J Epidemiol 2007; 166(8):924-31.
99. Von Low EC, Perabo , Siener R, Muller SC. Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data. In Vivo 2007; 21 (2):189-204.
100. MacRae HS, Mefferd KM. Dietary antioxidant supplementation combined with quercetin improves cycling time trial performance. Int J Sport Nutr Exerc Metab 2006; 16(4):405-19.
101. Nieman DC. Immunonutrition support for athletes. Nutr Rev 2008; 66(6):310-20.
102. Nieman DC, Henson DA, Davis JM, et al. Quercetin's influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol 2007; 103(5):1728-35.
103. McAnulty SR, McAnulty LS, Nieman DC, et al. Chronic quercetin ingestion and exercise-induced oxidative damage and inflammation. Appl Physiol Nutr Metab 2008; 33(2):254-62.
104. Valensi P, Le Devehat C, Richard JL, et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications 2005; 19(5):247-53.
105. Shoskes D, Lapierre C, Cruz-Correa M, et al. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation:a randomized placebo controlled trial. Transplantation 2005; 80(11):1556-9.
1. 李荟元等.新编瘢痕学.第四军医大学出版社[M]2003.
2. Reish RG, Eriksson E. Scar treatments:preclinical and clinical studies. J Am Coll Surg 2008; 206(4):719-30.
3. Wolfram D, Tzankov A, Pulzl P, Piza-Katzer H. Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg 2009; 35(2):171-81.
4. Bischoff SC. Quercetin:potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008; 11(6):733-40.
5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137(11):2405-11.
6. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype:a double-blinded, placebo-controlled cross-over study. Br J Nutr 2009:1-10.
7. Phan TT, Sun L, Bay BH, et al. Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro: therapeutic implication for excessive scarring. J Trauma 2003; 54(6):1212-24.
8. Phan TT, See P, Tran E, et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin:its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol 2003; 148(3):544-52.
9. Phan TT, Lim IJ, Sun L, et al. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci 2003; 33(3):192-4.
10. Phan TT, Lim IJ, Chan SY, et al. Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin:implications for the treatment of excessive scars. J Trauma 2004; 57(5):1032-7.
11. 吴兴成.槲皮素对瘢痕疙瘩成纤维细胞胶原合成的影响.整形再造外科杂志2005；2(3)：137-140.
12. Long X, Zeng X, Zhang FQ, Wang XJ. Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts. Chin Med Sci J 2006;21(3):179-83.
13. Morris DE, Wu L, Zhao LL, et al. Acute and chronic animal models for excessive dermal scarring:quantitative studies. Plast Reconstr Surg 1997; 100(3):674-81.
14. 李荟元,刘建波,夏炜等.增生性瘢痕动物实验模型的建立与应用.中华整形外科杂志2001；17(5)：276-278.
15. 毛维翰,方丽,吴伊旋.积雪苷治疗皮肤病的临床多中心试验.新药与临床1997；16(3)：133-136.
16. 赵亮,方方,王焱等.手术后放疗加口服积雪苷治疗瘢痕疙瘩的临床研究.中华皮肤科杂志2003；36(6)：342-344.
17. Ju-Lin X, Shao-Hai Q, Tian-Zeng L, et al. Effect of asiaticoside on hypertrophic scar in the rabbit ear model. J Cutan Pathol 2009; 36(2):234-9.
18. Kopp J, Preis E, Said H, et al. Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts. J Biol Chem 2005; 280(22):21570-6.
19. Saulis AS, Mogford JH, Mustoe TA. Effect of Mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002; 110(1):177-83; discussion 184-6.
20. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars:prospective double-blinded study. Dermatol Surg 2006; 32(2):193-7.
21. Ramos ML, Gragnani A, Ferreira LM. Is there an ideal animal model to study hypertrophic scarring? J Burn Care Res 2008; 29(2):363-8.
22. Shetlar MR, Shetlar CL, Hendricks L, Kischer CW. The use of athymic nude mice for the study of human keloids. Proc Soc Exp Biol Med 1985; 179(4):549-52.
23. Kischer CW, Sheridan D, Pindur J. Use of nude (athymic) mice for the study of hypertrophic scars and keloids:vascular continuity between mouse and implants. Anat Rec 1989; 225(3):189-96.
24. Hayward PG LH, Evans MJ et al A model of human keloid using the nude (athymic) rat Surg Forum 1991; 42:612-615.
25. Polo M, Kim YJ, Kucukcelebi A, et al. An in vivo model of human proliferative scar. J Surg Res 1998; 74(2):187-95.
26. 鲁峰,高建华.携带Fas基因重组腺病毒治疗瘢痕疙瘩的体内实验研究.中华外科杂志2007；45(15)：1058-1060.
27. Hillmer MP, MacLeod SM. Experimental keloid scar models:a review of methodological issues. J Cutan Med Surg 2002; 6(4):354-9.
28. Hochman B, Vilas Boas FC, Mariano M, Ferreiras LM. Keloid heterograft in the hamster (Mesocricetus auratus) cheek pouch, Brazil. Acta Cir Bras 2005; 20(3):200-12.
29. Aksoy MH, Vargel I, Canter IH, et al. A new experimental hypertrophic scar model in guinea pigs. Aesthetic Plast Surg 2002; 26(5):388-96.
30. Matsumura H, Engrav LH, Gibran NS, et al. Cones of skin occur where hypertrophic scar occurs. Wound Repair Regen 2001; 9(4):269-77.
31. Zhu KQ, Engrav LH, Gibran NS, et al. The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin. Burns 2003; 29(7):649-64.
32. Xie Y, Zhu KQ, Deubner H, et al. The microvasculature in cutaneous wound healing in the female red Duroc pig is similar to that in human hypertrophic scars and different from that in the female Yorkshire pig. J Burn Care Res 2007; 28(3):500-6.
33. Stewart CJ, Gallant-Behm CL, Forrester K, et al. Kinetics of blood flow during healing of excisional full-thickness skin wounds in pigs as monitored by laser speckle perfusion imaging. Skin Res Technol 2006; 12(4):247-53.
34. Harunari N, Zhu KQ, Armendariz RT, et al. Histology of the thick scar on the female, red Duroc pig:final similarities to human hypertrophic scar. Burns 2006; 32(6):669-77.
35. Gallant-Behm CL, Reno C, Tsao H, Hart DA. Genetic involvement in skin wound healing and scarring in domestic pigs:assessment of molecular expression patterns in (Yorkshire x Red Duroc) x Yorkshire backcross animals. J Invest Dermatol 2007; 127(1):233-44.
36. Liang Z, Xie CY, Lin HB, et al. [Pathomorphological observation of the hypertrophic scar induced by injury to conical structure in female red Duroc pig]. Zhonghua Shao Shang Za Zhi 2006; 22(1):29-32.
37. Gallant-Behm CL, Olson ME, Hart DA. Cytokine and growth factor mRNA expression patterns associated with the hypercontracted, hyperpigmented healing phenotype of red duroc pigs:a model of abnormal human scar development? J Cutan Med Surg 2005; 9(4):165-77.
38. Gallant-Behm CL, Hart DA. Genetic analysis of skin wound healing and scarring in a porcine model. Wound Repair Regen 2006; 14(1):46-54.
39. Gallant-Behm CL, Tsao H, Reno C, et al. Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs:evidence for genetic inheritance of wound phenotype. Burns 2006; 32(2):180-93.
40. Zhu KQ, Engrav LH, Armendariz R, et al. Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar. Burns 2005; 31(1):5-10.
41. Zhu KQ, Engrav LH, Tamura RN, et al. Further similarities between cutaneous scarring in the female, red Duroc pig and human hypertrophic scarring. Burns 2004; 30(6):518-30.
42. Gallant CL, Olson ME, Hart DA. Molecular, histologic, and gross phenotype of skin wound healing in red Duroc pigs reveals an abnormal healing phenotype of hypercontracted, hyperpigmented scarring. Wound Repair Regen 2004; 12(3):305-19.
43. Liang Z, Engrav LH, Muangman P, et al. Nerve quantification in female red Duroc pig (FRDP) scar compared to human hypertrophic scar. Burns 2004; 30(1):57-64.
44. 李荟元,刘建波,兰海.建立增生性瘢痕动物实验模型.第四军医大学学报1998：19：665-657.
45. Kryger ZB, Sisco M, Roy NK, et al. Temporal expression of the transforming growth factor-Beta pathway in the rabbit ear model of wound healing and scarring. J Am Coll Surg 2007; 205(1):78-88.
46. Marcus JR, Tyrone JW, Bonomo S, et al. Cellular mechanisms for diminished scarring with aging. Plast Reconstr Surg 2000; 105(5):1591-9.
47. Saulis AS, Chao JD, Telser A, et al. Silicone occlusive treatment of hypertrophic scar in the rabbit model. Aesthet Surg J 2002; 22(2):147-153.
48. Kim I, Mogford JE, Witschi C, et al. Inhibition of prolyl 4-hydroxylase reduces scar hypertrophy in a rabbit model of cutaneous scarring. Wound Repair Regen 2003;11(5):368-72.
49. Reid RR, Mogford JE, Butt R, et al. Inhibition of procollagen C-proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring. Wound Repair Regen 2006; 14(2):138-41.
50. Lu L, Saulis AS, Liu WR, et al. The temporal effects of anti-TGF-betal,2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation. J Am Coll Surg 2005; 201(3):391-7.
51. Lee JP, Jalili RB, Tredget EE, et al. Antifibrogenic effects of liposome-encapsulated IFN-alpha2b cream on skin wounds in a fibrotic rabbit ear model. J Interferon Cytokine Res 2005; 25(10):627-31.
52. Xie JL, Bian HN, Qi SH, et al. Basic fibroblast growth factor (bFGF) alleviates the scar of the rabbit ear model in wound healing. Wound Repair Regen 2008; 16(4):576-81.
53. Reid RR, Roy N, Mogford JE, et al. Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor II. J Plast Reconstr Aesthet Surg 2007; 60(1):64-72; discussion 73-4.
54. Sisco M, Kryger ZB, O'Shaughnessy KD, et al. Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo. Wound Repair Regen 2008; 16(5):661-73.
55. Henry SL, Concannon MJ, Kaplan PA, Diaz-Arias AA. The inhibitory effect of minocycline on hypertrophic scarring. Plast Reconstr Surg 2007; 120(1):80-8; discussion 89-90.
56. 张涛,荣新洲、杨荣华等.积雪草苷对增生性瘢痕中转化生长因子-β mRNA及基质金属蛋白酶类表达的影响.南方医科大学学报2006；26(1)：67-70.
57. 张涛、利天增、祈少海等.积雪草苷对烧伤创面愈合中细胞周期蛋白、增殖细胞核抗原表达的影响.中华实验外科杂志2005；22(1)：43-45.
58. Qi SH, Xie JL, Pan S, et al. Effects of asiaticoside on the expression of Smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts. Clin Exp Dermatol 2008;33(2):171-5.
59. Kimura Y, Sumiyoshi M, Samukawa K, et al. Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism. Eur J Pharmacol 2008; 584(2-3):415-23.
60. Lu L, Ying K, Wei S, et al. Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis. Br J Dermatol 2004; 151(3):571-8.
61. Kloeters O, Tandara A, Mustoe TA. Hypertrophic scar model in the rabbit ear:a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction. Wound Repair Regen 2007; 15 Suppl 1:S40-5.
62. 向军,王志勇,贾生贤等.一种增生性瘢痕动物模型的建立.中华烧伤杂志2004；20(5)：281-283.
63. 朱桂英,徐斌,蔡景龙.兔耳模型解剖特点与成功建立增生性瘢痕模型的相关性实验研究.中华整形外科杂志2008；24(3)：216-219.
64. 冯登超,杨喜明,薛宏斌等.建立更加稳定和有效的兔耳瘢痕模型.中国美容医学2009；18(2)：191-194.
65. 蔡虹,顾瑛,曾晶等.光动力疗法对兔耳增生性瘢痕作用的初步研究.中华 整形外科杂志2007；23(5)：425-427.
66. Jalili T, Carlstrom J, Kim S, et al. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 2006; 47(4):531-41.
67. Yamamoto Y, Oue E. Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci Biotechnol Biochem 2006; 70(4):933-9.
68. Duarte J, Perez-Palencia R, Vargas F, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 2001; 133(1):117-24.
69. Duarte J, Jimenez R, O'Valle F, et al. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 2002; 20(9):1843-54.
70. 赵维中,戴俐明,方明等.槲皮素在兔体内的药代动力学.中国药理学通报1992(6)：452-455.
71. Choi JS, Han HK. The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits. J Pharm Pharmacol 2004; 56(12):1537-42.
72. Choi JS, Li X. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits. Int J Pharm 2005; 297(1-2):1-8.
73. Juzwiak S, Wojcicki J, Mokrzycki K, et al. Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits. Pharmacol Rep 2005; 57(5):604-9.
74. Boots AW, Drent M, Swennen EL, et al. Antioxidant status associated with inflammation in sarcoidosis:a potential role for antioxidants. Respir Med 2009; 103(3):364-72.
75. Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol 2001; 7(1):44-6.
76. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category Ⅲ chronic prostatitis:a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999; 54(6):960-3.
77. Shoskes D, Lapierre C, Cruz-Correa M, et al. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation:a randomized placebo controlled trial. Transplantation 2005; 80(11):1556-9.
2. Johannot L, Somerset SM. Age-related variations in flavonoid intake and sources in the Australian population. Public Health Nutr 2006; 9(8):1045-54.
3. Bischoff SC. Quercetin:potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008;11(6):733-40.
4. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype:a double-blinded, placebo-controlled cross-over study. Br J Nutr 2009:1-10.
5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137(11):2405-11.
6. Theoharides TC, Bielory L. Mast cells and mast cell mediators as targets of dietary supplements. Ann Allergy Asthma Immunol 2004; 93(2 Suppl 1):S24-34.
7. Hollman PC, van Trijp JM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997; 418(1-2):152-6.
8. Murota K, Shimizu S, Chujo H, et al. Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2. Arch Biochem Biophys 2000; 384(2):391-7.
9. Graf BA, Ameho C, Dolnikowski GG, et al. Rat gastrointestinal tissues metabolize quercetin. J Nutr 2006; 136(1):39-44.
10. Murota K, Terao J. Quercetin appears in the lymph of unanesthetized rats as its phase Ⅱ metabolites after administered into the stomach. FEBS Lett 2005; 579(24):5343-6.
11. Oliveira EJ, Watson DG. In vitro glucuronidation of kaempferol and quercetin by human UGT-1A9 microsomes. FEBS Lett 2000; 471(1):1-6.
12. Boersma MG, van der Woude H, Bogaards J, et al. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chem Res Toxicol 2002; 15(5):662-70.
13. Olthof MR, Hollman PC, Buijsman MN, et al. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 2003; 133(6):1806-14.
14. Chen X, Yin OQ, Zuo Z, Chow MS. Pharmacokinetics and modeling of quercetin and metabolites. Pharm Res 2005; 22(6):892-901.
15. Walle T, Walle UK, Halushka PV. Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 2001; 131(10):2648-52.
16. Egert S, Wolffram S, Bosy-Westphal A, et al. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr 2008; 138(9):1615-21.
17. de Boer VC, Dihal AA, van der Woude H, et al. Tissue distribution of quercetin in rats and pigs. J Nutr 2005; 135(7):1718-25.
18. Wang L, Morris ME. Liquid chromatography-tandem mass spectroscopy assay for quercetin and conjugated quercetin metabolites in human plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 821(2):194-201.
19. Cross HJ, Tilby M, Chipman JK, et al. Effect of quercetin on the genotoxic potential of cisplatin. Int J Cancer 1996; 66(3):404-8.
20. Bjeldanes LF, Chang GW. Mutagenic activity of quercetin and related compounds. Science 1977; 197(4303):577-8.
21. Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med 2005; 16(2):275-8.
22. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category Ⅲ chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999; 54(6):960-3.
23. Lozoya X, Reyes-Morales H, Chavez-Soto MA, et al. Intestinal anti-spasmodic effect of a phytodrug of Psidium guajava folia in the treatment of acute diarrheic disease. J Ethnopharmacol 2002;83(1-2):19-24.
24. Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996; 2(4):659-68.
25. Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food ChemToxicol 2007; 45(11):2179-205.
26. Boots AW, Haenen GR, Bast A. Health effects of quercetin:from antioxidant to nutraceutical. Eur J Pharmacol 2008; 585(2-3):325-37.
27. Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 1994; 16(6):845-50.
28. Haenen GR, Bast A. Nitric oxide radical scavenging of flavonoids. Methods Enzymol 1999; 301:490-503.
29. Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 1997; 236(3):591-3.
30. Loke WM, Proudfoot JM, McKinley AJ, et al. Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 2008; 56(10):3609-15.
31. Shutenko Z, Henry Y, Pinard E, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 1999; 57(2):199-208.
32. Huk I, Brovkovych V, Nanobash Vili J, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury:an experimental study. Br J Surg 1998; 85(8):1080-5.
33. Zhu JX, Wang Y, Kong LD, et al. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004; 93(1):133-40.
34. Bindoli A, Valente M, Cavallini L. Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity. Pharmacol Res Commun 1985; 17(9):831-9.
35. Emura K, Yokomizo A, Toyoshi T, Moriwaki M. Effect of enzymatically modified isoquercitrin in spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 2007; 53(1):68-74.
36. Jalili T, Carlstrom J, Kim S, et al. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 2006; 47(4):531-41.
37. Duarte J, Jimenez R, O'Valle F, et al. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 2002; 20(9):1843-54.
38. Perez-Vizcaino F, Duarte J, Jimenez R, et al. Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 2009; 61(1):67-75.
39. Rivera L, Moron R, Sanchez M, et al. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring) 2008; 16(9):2081-7.
40. Ahn J, Lee H, Kim S, et al. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 2008; 373(4):545-9.
41. Sheu JR, Hsiao G, Chou PH, et al. Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets. J Agric Food Chem 2004; 52(14):4414-8.
42. Hubbard GP, Stevens JM, Cicmil M, et al. Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J Thromb Haemost 2003; 1(5):1079-88.
43. Pignatelli P, Di Santo S, Carnevale R, Violi F. The polyphenols quercetin and catechin synergize in inhibiting platelet CD40L expression. Thromb Haemost 2005; 94(4):888-9.
44. Fan PS, Gu ZL, Liang ZQ. Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro. Acta Pharmacol Sin 2001; 22(9):857-60.
45. Ko WC, Wang HL, Lei CB, et al. Mechanisms of relaxant action of 3-O-methylquercetin in isolated guinea pig trachea. Planta Med 2002; 68(1):30-5.
46. Dell'Agli M, Maschi O, Galli GV, et al. Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr 2008; 99(5):945-51.
47. Pearce FL, Befus AD, Bienenstock J. Mucosal mast cells. Ⅲ. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol 1984; 73(6):819-23.
48. Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 2000;30(4):501-8.
49. Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation. J Biol Regul Homeost Agents 2006; 20(3-4):47-52.
50. Kempuraj D, Castellani ML, Petrarca C, et al. Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Clin Exp Med 2006; 6(4):150-6.
51. Bureau G, Longpre F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res 2008; 86(2):403-10.
52. Kumazawa Y, Kawaguchi K, Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha. Curr Pharm Des 2006; 12(32):4271-9.
53. Lee KW, Kang NJ, Heo YS, et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine. Cancer Res 2008; 68(3):946-55.
54. Hamalainen M, Nieminen R, Vuorela P, et al. Anti-inflammatory effects of flavonoids:genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm 2007; 2007:45673.
55. Hirpara KV, Aggarwal P, Mukherjee AJ, et al. Quercetin and its derivatives:synthesis, pharmacological uses with special emphasis on anti-tumor properties and prodrug with enhanced bio-availability. Anticancer Agents Med Chem 2009; 9(2):138-61.
56. Wong SP, Li J, Shen P, et al. Ultrasensitive cell-based bioassay for the measurement of global estrogenic activity of flavonoid mixtures revealing additive, restrictive, and enhanced actions in binary and higher order combinations. Assay Drug Dev Technol 2007; 5(3):355-62.
57. van der Woude H, Ter Veld MG, Jacobs N, et al. The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol Nutr Food Res 2005; 49(8):763-71.
58. Schlachterman A, Valle F, Wall KM, et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol 2008;1(1):19-27.
59. Yamashita N, Kawanishi S. Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin. Free Radic Res 2000; 33(5):623-33.
60. Cantero G, Campanella C, Mateos S, Cortes F. Topoisomerase Ⅱ inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin. Mutagenesis 2006; 21(5):321-5.
61. Aherne SA, O'Brien NM. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000; 29(6):507-14.
62. Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett 2008; 269(2):315-25.
63. Psahoulia FH, Drosopoulos KG, Doubravska L, et al. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther 2007; 6(9):2591-9.
64. Chen W, Wang X, Zhuang J, et al. Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells. Carcinogenesis 2007; 28(10):2114-21.
65. Kim YH, Lee YJ. TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation. J Cell Biochem 2007; 100(4):998-1009.
66. Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005; 280(7):5636-45.
67. Xing N, Chen Y, Mitchell SH, Young CY. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis 2001; 22(3):409-14.
68. Morris JD, Pramanik R, Zhang X, et al. Selenium-or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity. Cancer Lett 2006; 239(1):111-22.
69. Phan TT, Sun L, Bay BH, et al. Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro:therapeutic implication for excessive scarring. J Trauma 2003; 54(6):1212-24.
70. Phan TT, See P, Tran E, et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin:its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol 2003; 148(3):544-52.
71. Phan TT, Lim IJ, Sun L, et al. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci 2003; 33(3):192-4.
72. Phan TT, Lim IJ, Chan SY, et al. Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin:implications for the treatment of excessive scars. J Trauma 2004; 57(5):1032-7.
73. Long X, Zeng X, Zhang FQ, Wang XJ. Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts. Chin Med Sci J 2006; 21(3):179-83.
74. Saulis AS, Mogford JH, Mustoe TA. Effect of Mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002; 110(1):177-83; discussion 184-6.
75. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars:prospective double-blinded study. Dermatol Surg 2006; 32(2):193-7.
76. Cushnie TP, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents 2005; 26(5):343-56.
77. Spedding G, Ratty A, Middleton E, Jr. Inhibition of reverse transcriptases by flavonoids. Antiviral Res 1989;12(2):99-110.
78. Davis JM, Murphy EA, McClellan JL, et al. Quercetin reduces susceptibility to influenza infection following stressful exercise. Am J Physiol Regul Integr Comp Physiol 2008; 295(2):R505-9.
79. Plaper A, Golob M, Hafner I, et al. Characterization of quercetin binding site on DNA gyrase. Biochem Biophys Res Commun 2003; 306(2):530-6.
80. Gonzalez-Segovia R, Quintanar JL, Salinas E, et al. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol 2008; 43(6):441-7.
81. Lines TC, Ono M. FRS 1000, an extract of red onion peel, strongly inhibits phosphodiesterase 5 A (PDE 5A). Phytomedicine 2006; 13(4):236-9.
82. Xin ZC, Kim EK, Lin CS, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl 2003; 5(1):15-8.
83. Wang H, Liu Y, Huai Q, et al. Multiple conformations of phosphodiesterase-5:implications for enzyme function and drug development. J Biol Chem 2006; 281(30):21469-79.
84. Hu HL, Forsey RJ, Blades TJ, et al. Antioxidants may contribute in the fight against ageing:an in vitro model. Mech Ageing Dev 2000; 121(1-3):217-30.
85. Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic Res 2006; 40(10):1054-65.
86. Chopra M, Fitzsimons PE, Strain JJ, et al. Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations. Clin Chem 2000; 46(8 Pt 1):1162-70.
87. Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost 2004; 2(12):2138-45.
88. Hubbard GP, Wolffram S, de Vos R, et al. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man:a pilot study. Br J Nutr 2006; 96(3):482-8.
89. Mardla V, Kobzar G, Samel N. Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin. Platelets 2004; 15(5):319-24.
90. Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol 2001; 7(1):44-6.
91. Cermak R, Vujicic Z, Kuhn G, Wolffram S. The secretory response of the rat colon to the flavonol quercetin is dependent on Ca2+-calmodulin. Exp Physiol 2000; 85(3):255-61.
92. Cermak R, Follmer U, Wolffram S. Dietary flavonol quercetin induces chloride secretion in rat colon. Am J Physiol 1998; 275(5 Pt 1):G1166-72.
93. Kim H, Kong H, Choi B, et al. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease. Pharm Res 2005; 22(9):1499-509.
94. Rao CV, Vijayakumar M. Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin, on experimental reflux oesophagitis in rats. Eur J Pharmacol 2008; 589(l-3):233-8.
95. Boots AW, Drent M, Swennen EL, et al. Antioxidant status associated with inflammation in sarcoidosis:a potential role for antioxidants. Respir Med 2009; 103(3):364-72.
96. Hirvonen T, Virtamo J, Korhonen P, et al. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control 2001;12(9):789-96.
97. Gates MA, Tworoger SS, Hecht JL, et al. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer 2007; 121(10):2225-32.
98. Nothlings U, Murphy SP, Wilkens LR, et al. Flavonols and pancreatic cancer risk:the multiethnic cohort study. Am J Epidemiol 2007; 166(8):924-31.
99. Von Low EC, Perabo , Siener R, Muller SC. Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data. In Vivo 2007; 21 (2):189-204.
100. MacRae HS, Mefferd KM. Dietary antioxidant supplementation combined with quercetin improves cycling time trial performance. Int J Sport Nutr Exerc Metab 2006; 16(4):405-19.
101. Nieman DC. Immunonutrition support for athletes. Nutr Rev 2008; 66(6):310-20.
102. Nieman DC, Henson DA, Davis JM, et al. Quercetin's influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol 2007; 103(5):1728-35.
103. McAnulty SR, McAnulty LS, Nieman DC, et al. Chronic quercetin ingestion and exercise-induced oxidative damage and inflammation. Appl Physiol Nutr Metab 2008; 33(2):254-62.
104. Valensi P, Le Devehat C, Richard JL, et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications 2005; 19(5):247-53.
105. Shoskes D, Lapierre C, Cruz-Correa M, et al. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation:a randomized placebo controlled trial. Transplantation 2005; 80(11):1556-9.
1. 李荟元等.新编瘢痕学.第四军医大学出版社[M]2003.
2. Reish RG, Eriksson E. Scar treatments:preclinical and clinical studies. J Am Coll Surg 2008; 206(4):719-30.
3. Wolfram D, Tzankov A, Pulzl P, Piza-Katzer H. Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg 2009; 35(2):171-81.
4. Bischoff SC. Quercetin:potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008; 11(6):733-40.
5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137(11):2405-11.
6. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype:a double-blinded, placebo-controlled cross-over study. Br J Nutr 2009:1-10.
7. Phan TT, Sun L, Bay BH, et al. Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro: therapeutic implication for excessive scarring. J Trauma 2003; 54(6):1212-24.
8. Phan TT, See P, Tran E, et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin:its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol 2003; 148(3):544-52.
9. Phan TT, Lim IJ, Sun L, et al. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci 2003; 33(3):192-4.
10. Phan TT, Lim IJ, Chan SY, et al. Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin:implications for the treatment of excessive scars. J Trauma 2004; 57(5):1032-7.
11. 吴兴成.槲皮素对瘢痕疙瘩成纤维细胞胶原合成的影响.整形再造外科杂志2005；2(3)：137-140.
12. Long X, Zeng X, Zhang FQ, Wang XJ. Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts. Chin Med Sci J 2006;21(3):179-83.
13. Morris DE, Wu L, Zhao LL, et al. Acute and chronic animal models for excessive dermal scarring:quantitative studies. Plast Reconstr Surg 1997; 100(3):674-81.
14. 李荟元,刘建波,夏炜等.增生性瘢痕动物实验模型的建立与应用.中华整形外科杂志2001；17(5)：276-278.
15. 毛维翰,方丽,吴伊旋.积雪苷治疗皮肤病的临床多中心试验.新药与临床1997；16(3)：133-136.
16. 赵亮,方方,王焱等.手术后放疗加口服积雪苷治疗瘢痕疙瘩的临床研究.中华皮肤科杂志2003；36(6)：342-344.
17. Ju-Lin X, Shao-Hai Q, Tian-Zeng L, et al. Effect of asiaticoside on hypertrophic scar in the rabbit ear model. J Cutan Pathol 2009; 36(2):234-9.
18. Kopp J, Preis E, Said H, et al. Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts. J Biol Chem 2005; 280(22):21570-6.
19. Saulis AS, Mogford JH, Mustoe TA. Effect of Mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002; 110(1):177-83; discussion 184-6.
20. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars:prospective double-blinded study. Dermatol Surg 2006; 32(2):193-7.
21. Ramos ML, Gragnani A, Ferreira LM. Is there an ideal animal model to study hypertrophic scarring? J Burn Care Res 2008; 29(2):363-8.
22. Shetlar MR, Shetlar CL, Hendricks L, Kischer CW. The use of athymic nude mice for the study of human keloids. Proc Soc Exp Biol Med 1985; 179(4):549-52.
23. Kischer CW, Sheridan D, Pindur J. Use of nude (athymic) mice for the study of hypertrophic scars and keloids:vascular continuity between mouse and implants. Anat Rec 1989; 225(3):189-96.
24. Hayward PG LH, Evans MJ et al A model of human keloid using the nude (athymic) rat Surg Forum 1991; 42:612-615.
25. Polo M, Kim YJ, Kucukcelebi A, et al. An in vivo model of human proliferative scar. J Surg Res 1998; 74(2):187-95.
26. 鲁峰,高建华.携带Fas基因重组腺病毒治疗瘢痕疙瘩的体内实验研究.中华外科杂志2007；45(15)：1058-1060.
27. Hillmer MP, MacLeod SM. Experimental keloid scar models:a review of methodological issues. J Cutan Med Surg 2002; 6(4):354-9.
28. Hochman B, Vilas Boas FC, Mariano M, Ferreiras LM. Keloid heterograft in the hamster (Mesocricetus auratus) cheek pouch, Brazil. Acta Cir Bras 2005; 20(3):200-12.
29. Aksoy MH, Vargel I, Canter IH, et al. A new experimental hypertrophic scar model in guinea pigs. Aesthetic Plast Surg 2002; 26(5):388-96.
30. Matsumura H, Engrav LH, Gibran NS, et al. Cones of skin occur where hypertrophic scar occurs. Wound Repair Regen 2001; 9(4):269-77.
31. Zhu KQ, Engrav LH, Gibran NS, et al. The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin. Burns 2003; 29(7):649-64.
32. Xie Y, Zhu KQ, Deubner H, et al. The microvasculature in cutaneous wound healing in the female red Duroc pig is similar to that in human hypertrophic scars and different from that in the female Yorkshire pig. J Burn Care Res 2007; 28(3):500-6.
33. Stewart CJ, Gallant-Behm CL, Forrester K, et al. Kinetics of blood flow during healing of excisional full-thickness skin wounds in pigs as monitored by laser speckle perfusion imaging. Skin Res Technol 2006; 12(4):247-53.
34. Harunari N, Zhu KQ, Armendariz RT, et al. Histology of the thick scar on the female, red Duroc pig:final similarities to human hypertrophic scar. Burns 2006; 32(6):669-77.
35. Gallant-Behm CL, Reno C, Tsao H, Hart DA. Genetic involvement in skin wound healing and scarring in domestic pigs:assessment of molecular expression patterns in (Yorkshire x Red Duroc) x Yorkshire backcross animals. J Invest Dermatol 2007; 127(1):233-44.
36. Liang Z, Xie CY, Lin HB, et al. [Pathomorphological observation of the hypertrophic scar induced by injury to conical structure in female red Duroc pig]. Zhonghua Shao Shang Za Zhi 2006; 22(1):29-32.
37. Gallant-Behm CL, Olson ME, Hart DA. Cytokine and growth factor mRNA expression patterns associated with the hypercontracted, hyperpigmented healing phenotype of red duroc pigs:a model of abnormal human scar development? J Cutan Med Surg 2005; 9(4):165-77.
38. Gallant-Behm CL, Hart DA. Genetic analysis of skin wound healing and scarring in a porcine model. Wound Repair Regen 2006; 14(1):46-54.
39. Gallant-Behm CL, Tsao H, Reno C, et al. Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs:evidence for genetic inheritance of wound phenotype. Burns 2006; 32(2):180-93.
40. Zhu KQ, Engrav LH, Armendariz R, et al. Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar. Burns 2005; 31(1):5-10.
41. Zhu KQ, Engrav LH, Tamura RN, et al. Further similarities between cutaneous scarring in the female, red Duroc pig and human hypertrophic scarring. Burns 2004; 30(6):518-30.
42. Gallant CL, Olson ME, Hart DA. Molecular, histologic, and gross phenotype of skin wound healing in red Duroc pigs reveals an abnormal healing phenotype of hypercontracted, hyperpigmented scarring. Wound Repair Regen 2004; 12(3):305-19.
43. Liang Z, Engrav LH, Muangman P, et al. Nerve quantification in female red Duroc pig (FRDP) scar compared to human hypertrophic scar. Burns 2004; 30(1):57-64.
44. 李荟元,刘建波,兰海.建立增生性瘢痕动物实验模型.第四军医大学学报1998：19：665-657.
45. Kryger ZB, Sisco M, Roy NK, et al. Temporal expression of the transforming growth factor-Beta pathway in the rabbit ear model of wound healing and scarring. J Am Coll Surg 2007; 205(1):78-88.
46. Marcus JR, Tyrone JW, Bonomo S, et al. Cellular mechanisms for diminished scarring with aging. Plast Reconstr Surg 2000; 105(5):1591-9.
47. Saulis AS, Chao JD, Telser A, et al. Silicone occlusive treatment of hypertrophic scar in the rabbit model. Aesthet Surg J 2002; 22(2):147-153.
48. Kim I, Mogford JE, Witschi C, et al. Inhibition of prolyl 4-hydroxylase reduces scar hypertrophy in a rabbit model of cutaneous scarring. Wound Repair Regen 2003;11(5):368-72.
49. Reid RR, Mogford JE, Butt R, et al. Inhibition of procollagen C-proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring. Wound Repair Regen 2006; 14(2):138-41.
50. Lu L, Saulis AS, Liu WR, et al. The temporal effects of anti-TGF-betal,2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation. J Am Coll Surg 2005; 201(3):391-7.
51. Lee JP, Jalili RB, Tredget EE, et al. Antifibrogenic effects of liposome-encapsulated IFN-alpha2b cream on skin wounds in a fibrotic rabbit ear model. J Interferon Cytokine Res 2005; 25(10):627-31.
52. Xie JL, Bian HN, Qi SH, et al. Basic fibroblast growth factor (bFGF) alleviates the scar of the rabbit ear model in wound healing. Wound Repair Regen 2008; 16(4):576-81.
53. Reid RR, Roy N, Mogford JE, et al. Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor II. J Plast Reconstr Aesthet Surg 2007; 60(1):64-72; discussion 73-4.
54. Sisco M, Kryger ZB, O'Shaughnessy KD, et al. Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo. Wound Repair Regen 2008; 16(5):661-73.
55. Henry SL, Concannon MJ, Kaplan PA, Diaz-Arias AA. The inhibitory effect of minocycline on hypertrophic scarring. Plast Reconstr Surg 2007; 120(1):80-8; discussion 89-90.
56. 张涛,荣新洲、杨荣华等.积雪草苷对增生性瘢痕中转化生长因子-β mRNA及基质金属蛋白酶类表达的影响.南方医科大学学报2006；26(1)：67-70.
57. 张涛、利天增、祈少海等.积雪草苷对烧伤创面愈合中细胞周期蛋白、增殖细胞核抗原表达的影响.中华实验外科杂志2005；22(1)：43-45.
58. Qi SH, Xie JL, Pan S, et al. Effects of asiaticoside on the expression of Smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts. Clin Exp Dermatol 2008;33(2):171-5.
59. Kimura Y, Sumiyoshi M, Samukawa K, et al. Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism. Eur J Pharmacol 2008; 584(2-3):415-23.
60. Lu L, Ying K, Wei S, et al. Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis. Br J Dermatol 2004; 151(3):571-8.
61. Kloeters O, Tandara A, Mustoe TA. Hypertrophic scar model in the rabbit ear:a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction. Wound Repair Regen 2007; 15 Suppl 1:S40-5.
62. 向军,王志勇,贾生贤等.一种增生性瘢痕动物模型的建立.中华烧伤杂志2004；20(5)：281-283.
63. 朱桂英,徐斌,蔡景龙.兔耳模型解剖特点与成功建立增生性瘢痕模型的相关性实验研究.中华整形外科杂志2008；24(3)：216-219.
64. 冯登超,杨喜明,薛宏斌等.建立更加稳定和有效的兔耳瘢痕模型.中国美容医学2009；18(2)：191-194.
65. 蔡虹,顾瑛,曾晶等.光动力疗法对兔耳增生性瘢痕作用的初步研究.中华 整形外科杂志2007；23(5)：425-427.
66. Jalili T, Carlstrom J, Kim S, et al. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 2006; 47(4):531-41.
67. Yamamoto Y, Oue E. Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci Biotechnol Biochem 2006; 70(4):933-9.
68. Duarte J, Perez-Palencia R, Vargas F, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 2001; 133(1):117-24.
69. Duarte J, Jimenez R, O'Valle F, et al. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 2002; 20(9):1843-54.
70. 赵维中,戴俐明,方明等.槲皮素在兔体内的药代动力学.中国药理学通报1992(6)：452-455.
71. Choi JS, Han HK. The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits. J Pharm Pharmacol 2004; 56(12):1537-42.
72. Choi JS, Li X. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits. Int J Pharm 2005; 297(1-2):1-8.
73. Juzwiak S, Wojcicki J, Mokrzycki K, et al. Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits. Pharmacol Rep 2005; 57(5):604-9.
74. Boots AW, Drent M, Swennen EL, et al. Antioxidant status associated with inflammation in sarcoidosis:a potential role for antioxidants. Respir Med 2009; 103(3):364-72.
75. Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol 2001; 7(1):44-6.
76. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category Ⅲ chronic prostatitis:a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999; 54(6):960-3.
77. Shoskes D, Lapierre C, Cruz-Correa M, et al. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation:a randomized placebo controlled trial. Transplantation 2005; 80(11):1556-9.