绞股蓝皂甙对复发性口腔溃疡大鼠T淋巴细胞亚群和抗氧化酶的影响
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摘要
目的:
建立大鼠复发性口腔溃疡(ROU)动物模型,探讨T淋巴细胞亚群,氧自由基与复发性口腔溃疡发病机制的关系及观察绞股蓝皂甙对大鼠复发性口腔溃疡动物模型的免疫调节和抗氧化作用。为绞股蓝皂甙治疗复发性口腔溃疡的实验研究和临床应用提供一定的理论依据。
方法:
用免疫方法(异体大鼠口腔黏膜匀浆组织加完全弗氏佐剂脊柱两侧皮下注射)建立大鼠复发性口腔溃疡动物模型并观察大鼠的口腔表现。切取正常及溃疡大鼠的口腔黏膜组织,HE染色病理检查。将实验大鼠随机分为4组:正常对照组、模型组、左旋咪唑组和绞股蓝皂甙组。分别于造模后、给药后大鼠眼眶采血,用流式细胞仪检测大鼠外周血T淋巴细胞亚群CD4~+、CD8~+细胞比例及CD4~+/CD8~+比值;分别用黄嘌呤氧化酶法、DINB显色法和硫代巴比妥酸法检测大鼠血清中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)的活性和脂质氧化终产物丙二醛(MDA)的含量。
结果:
1.实验大鼠于第三次注射一周后开始出现口腔溃疡;病理组织检查见黏膜上皮内淋巴细胞浸润,溶解破溃,固有层内中性粒细胞、淋巴细胞及单核细胞等炎症细胞大量浸润,溃疡底部及上皮下毛细血管扩张充血,腺体增生形成溃疡。
2.模型组与正常对照组相比,大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+明显降低,有显著性差异(P<0.05),CD8~+也有降低但无显著性差异;实验大鼠给药后,绞股蓝皂甙组和左旋咪唑组与模型组相比,大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+明显升高(P<0.05),CD8~+也有升高但无显著性差异;两组之间比较没有显著性差异。
3.模型组与正常对照组相比,大鼠血清中SOD和GSHPx的活性明显降低,MDA含量明显升高,有显著性差异(P<0.05);实验大鼠给药后,左旋咪唑组与模型组相比,大鼠血清中SOD的活性升高,GSHPx活性和MDA含量降低,但无显著性差异;绞股蓝皂甙组与模型组相比,大鼠血清中SOD和GSHPx的活性明显升高,MDA含量明显降低,有显著性差异(P<0.05),两组之间比较有显著性差异(P<0.05)。
结论:
1.复发性口腔溃疡模型组大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+较正常对照组降低,进一步证实了复发性口腔溃疡的发病与T淋巴细胞亚群失衡有关。
2.复发性口腔溃疡模型组大鼠血清中SOD和GSHPx的活性较正常对照组降低、MDA含量较正常对照组升高,提示复发性口腔溃疡的发病与氧自由基损伤有关。
3.绞股蓝皂甙治疗后,CD4~+细胞比例及CD4~+/CD8~+较正常对照组升高,SOD和GSHPx的活性较正常对照组升高,MDA含量较正常对照组降低,绞股蓝皂甙对大鼠复发性口腔溃疡动物模型有一定的免疫调节和抗氧化作用,免疫调节作用与左旋咪唑无显著差异,但抗氧化作用明显优于左旋咪唑。
4.绞股蓝皂甙用于复发性口腔溃疡的治疗具有一定的开发前景。
Objective:
Established the rat’s recurrent oral ulceration(ROU)models and discussed the relationsip between T- lymphocyte substock,oxygen radical and the pathogenesis of recurrent oral ulceration and evaluated the immune regulation and antioxidative effects of Gypenoside(GPs) on ROU.In order to provide certain theory basis of Gypenoside(GPs)’s experiment and clinical research.
Methods:
Rats models of recurrent oral ulceration with immunology were established(Add Freund’s complete adjuvant(FCA) to galacta of health variant rat’s oral mucosa as the antigen, and injected it to two sides of spinal column);Cut the oral mucosa of normal and ulcer rats,and make Hematoxylin-eosin(HE) staining pathology examination;The rats were randomly divided into 4 groups,including control group,modelgroup,Levamisole group and Gypenoside group. Drawing blood from the eyes of rats while around the model was established and after administration.The changes of CD4~+,CD8~+ in blood were observed using flow - cytometre before and after the model as well as after the therapy.The activity of superoxide dismutase(SOD) was measured in all specimens of rats by xanthine oxidase method.The activity of glutathione peroxidase(GSHPx)was measured in all specimens of rats by DTNBdevelopment process.The activity of catalase(CAT) was measured in all specimens of rats by visible spectrometry.The contents of malondialdehyde(MDA) was measured in all specimens of rats by thiobarbituric acid method.
Results:
1.Histologically,infiltration of intraepithelial lymphocytes,dissolved ulceration,a large number of inflammatory cell infiltration in lamina propria,capillary congestion expansion,gland hyperplasia,the ulcers were formed.
2.Compared with control group, the values of CD4~+and CD4~+/CD8~+ showed significantly lower level in ROU rats (P<0.05),while CD8~+ not.After Levamisole and Gypenoside treatment,the values of CD4~+ and CD4~+/CD8~+ increased significantly (P<0.05),It did not show any significant difference among the two groups.
3.The activity of SOD and GSHPx of ROU rats was significantly lower than the control group (P<0.05).The contents of MDA was significantly higher than the control group(P<0.05).After treatment,The activity of SOD and GSHPx of Gypenoside group was significantly higher than the control group(P<0.05).The contents of MDA was significantly lower than the control group (P<0.05).The activity of SOD of Levamisole group was higher than the control group,but no significant difference.The activity of GSHPx and the contents of MDA was lower than the control group,but no significant difference.
Conclusion:
1.Compared with control group,the values of CD4~+ and CD4~+/CD8~+ showed significantly lower level in ROU rats,suggesting that The unbalance of T-lymphocyte substock may contribute to ROU incidence.
2.The activity of SOD and GSHPx of ROU rats was significantly lower than the control group. The contents of MDA was significantly higher than the control group,suggesting that oxygen radical may contribute to ROU incidence.
3.GPs had the immune regulation and antioxidative effects on experimental ROU rats,and the immune efficacy is as same as Levamisole,but the antioxidative effects excelled Levamisole.
4.GPs had definite developing prospect for curing ROU.
建立大鼠复发性口腔溃疡(ROU)动物模型,探讨T淋巴细胞亚群,氧自由基与复发性口腔溃疡发病机制的关系及观察绞股蓝皂甙对大鼠复发性口腔溃疡动物模型的免疫调节和抗氧化作用。为绞股蓝皂甙治疗复发性口腔溃疡的实验研究和临床应用提供一定的理论依据。
方法:
用免疫方法(异体大鼠口腔黏膜匀浆组织加完全弗氏佐剂脊柱两侧皮下注射)建立大鼠复发性口腔溃疡动物模型并观察大鼠的口腔表现。切取正常及溃疡大鼠的口腔黏膜组织,HE染色病理检查。将实验大鼠随机分为4组:正常对照组、模型组、左旋咪唑组和绞股蓝皂甙组。分别于造模后、给药后大鼠眼眶采血,用流式细胞仪检测大鼠外周血T淋巴细胞亚群CD4~+、CD8~+细胞比例及CD4~+/CD8~+比值;分别用黄嘌呤氧化酶法、DINB显色法和硫代巴比妥酸法检测大鼠血清中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)的活性和脂质氧化终产物丙二醛(MDA)的含量。
结果:
1.实验大鼠于第三次注射一周后开始出现口腔溃疡;病理组织检查见黏膜上皮内淋巴细胞浸润,溶解破溃,固有层内中性粒细胞、淋巴细胞及单核细胞等炎症细胞大量浸润,溃疡底部及上皮下毛细血管扩张充血,腺体增生形成溃疡。
2.模型组与正常对照组相比,大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+明显降低,有显著性差异(P<0.05),CD8~+也有降低但无显著性差异;实验大鼠给药后,绞股蓝皂甙组和左旋咪唑组与模型组相比,大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+明显升高(P<0.05),CD8~+也有升高但无显著性差异;两组之间比较没有显著性差异。
3.模型组与正常对照组相比,大鼠血清中SOD和GSHPx的活性明显降低,MDA含量明显升高,有显著性差异(P<0.05);实验大鼠给药后,左旋咪唑组与模型组相比,大鼠血清中SOD的活性升高,GSHPx活性和MDA含量降低,但无显著性差异;绞股蓝皂甙组与模型组相比,大鼠血清中SOD和GSHPx的活性明显升高,MDA含量明显降低,有显著性差异(P<0.05),两组之间比较有显著性差异(P<0.05)。
结论:
1.复发性口腔溃疡模型组大鼠外周血中CD4~+细胞比例及CD4~+/CD8~+较正常对照组降低,进一步证实了复发性口腔溃疡的发病与T淋巴细胞亚群失衡有关。
2.复发性口腔溃疡模型组大鼠血清中SOD和GSHPx的活性较正常对照组降低、MDA含量较正常对照组升高,提示复发性口腔溃疡的发病与氧自由基损伤有关。
3.绞股蓝皂甙治疗后,CD4~+细胞比例及CD4~+/CD8~+较正常对照组升高,SOD和GSHPx的活性较正常对照组升高,MDA含量较正常对照组降低,绞股蓝皂甙对大鼠复发性口腔溃疡动物模型有一定的免疫调节和抗氧化作用,免疫调节作用与左旋咪唑无显著差异,但抗氧化作用明显优于左旋咪唑。
4.绞股蓝皂甙用于复发性口腔溃疡的治疗具有一定的开发前景。
Objective:
Established the rat’s recurrent oral ulceration(ROU)models and discussed the relationsip between T- lymphocyte substock,oxygen radical and the pathogenesis of recurrent oral ulceration and evaluated the immune regulation and antioxidative effects of Gypenoside(GPs) on ROU.In order to provide certain theory basis of Gypenoside(GPs)’s experiment and clinical research.
Methods:
Rats models of recurrent oral ulceration with immunology were established(Add Freund’s complete adjuvant(FCA) to galacta of health variant rat’s oral mucosa as the antigen, and injected it to two sides of spinal column);Cut the oral mucosa of normal and ulcer rats,and make Hematoxylin-eosin(HE) staining pathology examination;The rats were randomly divided into 4 groups,including control group,modelgroup,Levamisole group and Gypenoside group. Drawing blood from the eyes of rats while around the model was established and after administration.The changes of CD4~+,CD8~+ in blood were observed using flow - cytometre before and after the model as well as after the therapy.The activity of superoxide dismutase(SOD) was measured in all specimens of rats by xanthine oxidase method.The activity of glutathione peroxidase(GSHPx)was measured in all specimens of rats by DTNBdevelopment process.The activity of catalase(CAT) was measured in all specimens of rats by visible spectrometry.The contents of malondialdehyde(MDA) was measured in all specimens of rats by thiobarbituric acid method.
Results:
1.Histologically,infiltration of intraepithelial lymphocytes,dissolved ulceration,a large number of inflammatory cell infiltration in lamina propria,capillary congestion expansion,gland hyperplasia,the ulcers were formed.
2.Compared with control group, the values of CD4~+and CD4~+/CD8~+ showed significantly lower level in ROU rats (P<0.05),while CD8~+ not.After Levamisole and Gypenoside treatment,the values of CD4~+ and CD4~+/CD8~+ increased significantly (P<0.05),It did not show any significant difference among the two groups.
3.The activity of SOD and GSHPx of ROU rats was significantly lower than the control group (P<0.05).The contents of MDA was significantly higher than the control group(P<0.05).After treatment,The activity of SOD and GSHPx of Gypenoside group was significantly higher than the control group(P<0.05).The contents of MDA was significantly lower than the control group (P<0.05).The activity of SOD of Levamisole group was higher than the control group,but no significant difference.The activity of GSHPx and the contents of MDA was lower than the control group,but no significant difference.
Conclusion:
1.Compared with control group,the values of CD4~+ and CD4~+/CD8~+ showed significantly lower level in ROU rats,suggesting that The unbalance of T-lymphocyte substock may contribute to ROU incidence.
2.The activity of SOD and GSHPx of ROU rats was significantly lower than the control group. The contents of MDA was significantly higher than the control group,suggesting that oxygen radical may contribute to ROU incidence.
3.GPs had the immune regulation and antioxidative effects on experimental ROU rats,and the immune efficacy is as same as Levamisole,but the antioxidative effects excelled Levamisole.
4.GPs had definite developing prospect for curing ROU.
引文
[1]Femiano F,Lanza A,Buonaiuto C,et al. Guidelines for diagnosis and management of aphthous stomatitis. Pediatr Infect Dis J, 2007,26(8):728-732.
[2]Babaee N,Mansourian A,Momen-Heravi F, et al.The efficacy of a paste containing Myrtus communis (Myrtle) in the management of recurrent aphthous stomatitis: a randomized controlled trial. Clin Oral Investig,2009,14(1):65-70.
[3]Zunt SL.Recurrent aphthous stomatitis.Dermatologic Clinics,2003,21(1):33-39.
[4]Akintoye SO,Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am, 2005,49(1): 31-47.
[5]李奉华,刘虹.复发性阿弗他溃疡致病因素及机制的研究进展.中国现代医学杂志,2003,13(7):41-43.
[6]Sistig S, Cekic-Arambasin A, Rabatic S, et al. Natural immunity in recurrent aphthous ulceration. J Oral Pathol Med, 2001,30(5):275-280.
[7]Bachtiar EW,Cornain S,Siregar B,et al.Decreased CD4+/CD8+ratio in major type of recurrent aphthous ulcers:comparing major to minor types of ulcers.Asian Pac J Allergy Immunol,1998 ,16(2-3):75-79.
[8]Scully C,Gorsky M,Lozada-Nur F.The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc,2003,134(2): 200-7.
[9]Beevi SS,Rasheed AM,Geetha A.Evaluation of oxidative stress and nitric oxide levels in patients with oral cavity cancer. Jpn J Clin Oncol,2004,34(7):379–85.
[10]Sezer E,Ozugurlu F,Ozyurt H,et al.Lipid peroxidation and antioxidant status in lichen planus. Clin Exp Dermatol,2007,32(4):430-4.
[11]Hoelzl C,Bichler J,Ferk F,et al. Methods for the detection of antioxidants which prevent age related diseases:a critical review with particular emphasis on human intervention studies.J Physiol Pharmacol,2005,56(2):49-64.
[12]Cimen MY,Kaya TI,Eskandari G,et al.Oxidant/antioxidant status in patients with recurrent aphthous stomatits.Clin Exp Dermatol,2003,28(6):647-50.
[13]Karincaoglu Y,Batcioglu K,Erdem T,et al. The levels of plasma and salivary antioxidants in the patient with recurrent aphthous stomatitis.J Oral Pathol Med,2005,34(1):7–12.
[14]马旭辉,孙黎飞.复发性阿弗他溃疡的基础研究与治疗现状.实用医药杂志,2006,23(10):12 64-1266.
[15]郭玉苏,梁文红.中医中药治疗复发性口疮的研究现状.国际口腔医学杂志,2008,35(增刊):184-192.
[16]李金青,杨洪军.绞股蓝的药理作用研究进展.中国现代药物应用,2009,3(7):189-190.
[17]苗爱群,刘书翰,王兰君.复发性口腔溃疡动物模型改进.中华口腔医学杂志,1994,9(29):299-301.
[18]陶学金,李明,冯爱慧,等.免疫方法建立复发性口腔溃疡动物模型.临床口腔医学杂志, 2004,20(1):53-54.
[19]程茜,刘建国,郭玉书,等.实验性SD大鼠ROU模型的建立.临床口腔医学杂志,2008,24(9): 563-565.
[20]Castellino F,Germain RN.Cooperation between CD4(+)and CD8(+)T cells:When,Where,and How.Annu Rev Immunol,2006,24:519-40.
[21]Prat A,Antel J.Pathogenesis of multiple sclerosis.Curr Opin Neurol,2005 ,18 (3):225-30.
[22]Sablotzki A,Ebel H,Muhling J,et al.Dysregulation of immane response following neurosurgical operations.Acta Anaesthesiol Scand,2000,44(1):82-7.
[23]孙鹏.淋巴细胞、细胞因子与复发性阿弗他溃疡.解放军医学杂志,2004,29(2):180-182.
[24]胡雁,NeilWS,PhilBS.复发性阿弗他溃疡患者淋巴细胞抑制功能的改变.中华口腔医学杂志,1998,33(2):103-105.
[25]孙黎飞,刘海军,于广远,等.复发性口腔溃疡患者的细胞免疫功能研究.中国免疫学杂志,2001,17(6):332-333.
[26]方豪,戴淳,方东,等.复发性口疮流式细胞分析T淋巴细胞亚群.口腔医学,2001,21(1):31- 32.
[27]Gunduz K,Ozturk G,Sozmen EY.Erythrocyte superoxide dismutase,catalase activities and plasma nitrite and nitrate levels in patients with Behcet’s disease and recurrent aphthous stomatitis.Clin Exp Dermatol,2004,29(2):176-9.
[28]Arikan S,Durusoy C,Akalin N,et al.Oxidant/antioxidant status in recurrent aphthous stomatitis.Oral Dis,2009,15(7):512-5.
[29]Momen-Beitollahi J,Mansourian A,Momen-Heravi F,et al.Assessment of salivary and serum antioxidant status in patients with recurrent aphthous stomatitis.Oral Medicine and Pathology,2010,15(4):e557-61.
[30]陈谦明.氧自由基对口腔黏膜损伤的动物实验研究-动物模型的形态和结构变化.华西口腔医学杂志,1993,(1):65-67.
[31]李秉琦.氧自由基对口腔黏膜损伤的动物实验研究-氧自由基对动物黏酶活性的影响.华西口腔医学杂志,1993(2):135-137.
[32]薄芯.生化复合黄腐酸、青黛和绞股蓝总甙对T淋巴细胞转化的影响.中国中医药科技,2003,10(6):351-352.
[33]段炳南,陈庆林.绞股蓝总皂甙对小鼠腹腔巨噬细胞内酶活性及吞噬功能的影响.江西医学院学报,2007,47(3):38-40.
[34]周俐,叶开和,任先达.绞股蓝总苷对免疫功能低下小鼠模型特异性免疫功能的影响.中华中医药学刊,2008,26(1):145-146.
[35]张青蓓,马俊江,曹之宪等.绞股蓝总皂苷对NCTC11637株HP延缓大鼠实验性胃溃疡愈合的治疗作用及其机制.中国药理学通报,1999,15(3):225-228.
[36]王宏涛,叶云,肖顺林等.绞股蓝乙酸乙酯提取物对胃溃疡大鼠胃黏膜血管活性物质的影响.中国中医急症,2008,17(10):1437-1438.
[1]干祖望.干氏耳鼻咽喉口腔科学.南京:江苏科学技术出版社,1990:278-280.
[2]梅武轩.劳绍贤教授从湿热论治复发性口腔溃疡的经验.陕西中医,2006,27(3):322-323.
[3]王跃才,张莲英,普曦娜,等.辨证分型治疗复发性口疮97例报告.云南中医中药杂志,2002, 23(2):30-31.
[4]李翠玉.复发性口疮证治体会.实用中医药杂志,2005,21(4):233.
[5]闫莉莉.活血化瘀方药治疗顽固性口腔溃疡11例.中国民间疗法,2006,14(8):36-37.
[6]李月斌,姜庆荣,王长洲.活血化瘀治疗复发性口腔溃疡33例.山东中医杂志,2003,22(3):153 -154.
[7]过伟峰,周仲瑛,汪红,等.口疮平口服液防治83例复发性口疮复发的临床研究.江苏中医,2002,23(9):9-11.
[8]詹家明,张晓钰.益气清热养阴活血法治疗复发性口腔溃疡30例.上海中医杂志,1998(7):32
[9]薛西林.马骏治疗慢性复发性口腔溃疡的经验.北京中医,2005,24(6):335-336.
[10]陈世友.辨治复发性口腔溃疡56例.中外健康文摘医药月刊, 2006,3(11):99-101.
[11]张军,刘金喜,张萍.辨证分型治疗复发性口腔溃疡46例.陕西中医,2005,26(6):533-534.
[12]程伟,王吉英.辨证治疗复发性口腔溃疡82例.中医药学刊,2005,23(4):744.
[13]王晓山,陈建灵,林茜,等.修疡口服液治疗复发性口疮100例临床研究.甘肃中医,2002,15 (4):24-25.
[14]鞠少斌,李冬莲.清火汤治疗复发性口腔溃疡的临床观察.医学理论与实践杂志,2007,20( 5):564-565.
[15]王红宇.半夏泻心汤化裁治疗复发性口腔溃疡98例.北京中医,2007,26(3):164-165.
[16]成正雄,刘卫平,肖志勇,等.滋阴降火汤治疗复发性口腔溃疡93例疗效观察.长沙医学院学报,2006,16(6):29-32.
[17]姜国平,彭清华,鹿小君.香砂六君子汤加味治疗复发性口腔溃疡40例.江西中医药,2007,( 6):38.
[18]韩燕,贺瀛.加味麦门冬汤治疗阴虚火旺型复发性口腔溃疡60例.中国中西医结合杂志, 2007,27(7):662.
[19]田乃定.黄连阿胶汤治疗复发性口腔溃疡疗效观察.山西中医,2003,19(2):46.
[20]周杰.乌梅丸治疗复发性口腔溃疡.湖北中医杂志,2003,25(8):45.
[21]过伟峰,周仲瑛,汪红,等.口疮平口服液防治72例复发性口疮复发的临床研究.江苏中医, 2002,23(9):9-11.
[22]王晓山,陈建灵,林茜,等.修疡口服液治疗复发性口疮100例临床研究.甘肃中医,2002,15( 4):24-25.
[23]李佩洲,常新华.口疮宁颗粒治疗阴虚火旺型复发性口疮的临床研究.辽宁中医杂志,2002,29(7):411.
[24]黄兆坤.口康饮治疗复发性口腔溃疡的研究.现代中西医结合杂志,2004,13(6):718-719.
[25]孙冰,刘国惠,姚源璋,等.愈溃膜、口宝含片分期治疗复发性口腔溃疡临床研究.山东中医杂志,2000,19(2):74-75.
[26]李彩凤,孙爱英.信青溃疡液治疗复发性口腔溃疡的临床观察.中医药学报,2003,31(6):44- 45.
[27]官纯寿,罗树星.中药喷雾剂治疗复发性口腔溃疡的临床研究.华中科技大学学报,2003,32 (5):558-560.
[28]李丽萍,王海霞,王幼.芪附汤治疗顽固性口腔溃疡45例.现代中西医结合杂志,2007,16( 11):1503.
[29]高洁萱.清肺养阴汤治疗复发性口腔溃疡.山西中医,2007,23(3):75.
[30]刘挺立,迟永利,纪金风,等.二黄汤治疗复发性口腔溃疡临床分析.山东中医药大学学报, 2004,28(3):212-213.
[31]赵敏,刘如霖,李永升.自拟三泰丸治疗复发性口腔溃疡85例.甘肃中医,2000,13(1):30.
[32]陈美南,宋敏,李富玉.自拟清疮汤治疗复发性口腔溃疡临床观察.中医药学刊,2005,23( 12):2297.
[33]苏涛,马旭东.口腔解毒汤治疗复发性阿弗他溃疡临床疗效观察.中国实验方剂学,2010,16 (7).
[34]陈敏,张振贤,吴丽丽,等.芪卿方治疗复发性口腔溃疡临床疗效观察.中国医药指南,2010,8 (6):77-79.
[35]耿平,杨洪凤,岳义国.青茶散治疗复发性口腔溃疡126例.实用中医内科杂志,2003,17(1): 56.
[36]贾文超,任学伟.中西药结合治疗复发性口疮50例.口腔医学,2005,25(4):221.
[37]刘海光,朱斌,张利平.口必健治疗复发性口疮的临床观察.黑龙江医学,2004,28(11):837- 838.
[38]贾泽宇,刘春子,米宏图.中药散剂治疗口腔溃疡的疗效观察.中国社区医师,2007,14(9):79.
[39]孙林琳.复方溃疡散治疗复发性口腔溃疡的疗效观察.口腔医学,2004,24(5):318-319.
[40]王虹,庞彬.芦荟散治疗复发性口疮.湖北中医杂志,2004,26(7):37.
[41]彭楚湘,李元聪.针刺配合中药治疗复发性口腔溃疡86例.湖南中医学院学报,2003,23(2) :51-52.
[42]董杨颖,邓晓莹.中药结合耳针治疗复发性口腔溃疡50例.中国中医药信息杂志,2004,11( 5):437.
[43]陈建灵.谈复发性口疮防治中的难点与对策.辽宁中医学院学报,2005,7(6):602-603.
[44]薛西林.马骏治疗慢性复发性口腔溃疡的经验.北京中医,2005,24(6):335-336.
[45]官纯寿,罗树星.中药喷雾剂治疗复发性口腔溃疡的临床研究.华中科技大学学报,2003,32(5):558-560.
[46]张兰海.雷公藤治疗频发复发性口疮的临床观察.口腔医学,2003,23(1):35-36.
[47]周杰.乌梅丸治疗复发性口腔溃疡30例临床观察.临床口腔医学杂志,2003,19(6):370- 371.
[48]孙林琳.六味地黄丸对复发性口疮患者细胞免疫功能影响的观察.实用口腔医学杂志, 2004,20(5):647-648.
[49]马文斌,步革,谢文忠,等.雷公藤多甙治疗复发性口疮的远期疗效与血清NO及NOS的变化.实用口腔医学杂志,2006,22(2):267-268.
[50]郭红云,刘秀玉.中药治疗复发性阿弗他溃疡免疫调节与疗效观察.中国民康医学,2006,18(6):434-435.
[51]王淑慧,严长宏.蒲黄一物散治疗阿弗他性口炎70例.新中医,2007,39(3):69-70.
[52]朱金晓,单莉英,刘志辉,等.黄芪治疗复发性阿弗他溃疡疗效分析及作用机理探讨.临床口腔医学杂志,2007,23(11):668-671.
[53]胡渝芳,张永忠.甘草泻心汤治疗复发性阿弗他溃疡的T淋巴细胞亚群变化.实用药物与临床,2008,11(2):68-69.
[54]朱康伟.贞芪扶正颗粒治疗复发性口疮52例.中医中药,2009,47(18):136-139.
[2]Babaee N,Mansourian A,Momen-Heravi F, et al.The efficacy of a paste containing Myrtus communis (Myrtle) in the management of recurrent aphthous stomatitis: a randomized controlled trial. Clin Oral Investig,2009,14(1):65-70.
[3]Zunt SL.Recurrent aphthous stomatitis.Dermatologic Clinics,2003,21(1):33-39.
[4]Akintoye SO,Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am, 2005,49(1): 31-47.
[5]李奉华,刘虹.复发性阿弗他溃疡致病因素及机制的研究进展.中国现代医学杂志,2003,13(7):41-43.
[6]Sistig S, Cekic-Arambasin A, Rabatic S, et al. Natural immunity in recurrent aphthous ulceration. J Oral Pathol Med, 2001,30(5):275-280.
[7]Bachtiar EW,Cornain S,Siregar B,et al.Decreased CD4+/CD8+ratio in major type of recurrent aphthous ulcers:comparing major to minor types of ulcers.Asian Pac J Allergy Immunol,1998 ,16(2-3):75-79.
[8]Scully C,Gorsky M,Lozada-Nur F.The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc,2003,134(2): 200-7.
[9]Beevi SS,Rasheed AM,Geetha A.Evaluation of oxidative stress and nitric oxide levels in patients with oral cavity cancer. Jpn J Clin Oncol,2004,34(7):379–85.
[10]Sezer E,Ozugurlu F,Ozyurt H,et al.Lipid peroxidation and antioxidant status in lichen planus. Clin Exp Dermatol,2007,32(4):430-4.
[11]Hoelzl C,Bichler J,Ferk F,et al. Methods for the detection of antioxidants which prevent age related diseases:a critical review with particular emphasis on human intervention studies.J Physiol Pharmacol,2005,56(2):49-64.
[12]Cimen MY,Kaya TI,Eskandari G,et al.Oxidant/antioxidant status in patients with recurrent aphthous stomatits.Clin Exp Dermatol,2003,28(6):647-50.
[13]Karincaoglu Y,Batcioglu K,Erdem T,et al. The levels of plasma and salivary antioxidants in the patient with recurrent aphthous stomatitis.J Oral Pathol Med,2005,34(1):7–12.
[14]马旭辉,孙黎飞.复发性阿弗他溃疡的基础研究与治疗现状.实用医药杂志,2006,23(10):12 64-1266.
[15]郭玉苏,梁文红.中医中药治疗复发性口疮的研究现状.国际口腔医学杂志,2008,35(增刊):184-192.
[16]李金青,杨洪军.绞股蓝的药理作用研究进展.中国现代药物应用,2009,3(7):189-190.
[17]苗爱群,刘书翰,王兰君.复发性口腔溃疡动物模型改进.中华口腔医学杂志,1994,9(29):299-301.
[18]陶学金,李明,冯爱慧,等.免疫方法建立复发性口腔溃疡动物模型.临床口腔医学杂志, 2004,20(1):53-54.
[19]程茜,刘建国,郭玉书,等.实验性SD大鼠ROU模型的建立.临床口腔医学杂志,2008,24(9): 563-565.
[20]Castellino F,Germain RN.Cooperation between CD4(+)and CD8(+)T cells:When,Where,and How.Annu Rev Immunol,2006,24:519-40.
[21]Prat A,Antel J.Pathogenesis of multiple sclerosis.Curr Opin Neurol,2005 ,18 (3):225-30.
[22]Sablotzki A,Ebel H,Muhling J,et al.Dysregulation of immane response following neurosurgical operations.Acta Anaesthesiol Scand,2000,44(1):82-7.
[23]孙鹏.淋巴细胞、细胞因子与复发性阿弗他溃疡.解放军医学杂志,2004,29(2):180-182.
[24]胡雁,NeilWS,PhilBS.复发性阿弗他溃疡患者淋巴细胞抑制功能的改变.中华口腔医学杂志,1998,33(2):103-105.
[25]孙黎飞,刘海军,于广远,等.复发性口腔溃疡患者的细胞免疫功能研究.中国免疫学杂志,2001,17(6):332-333.
[26]方豪,戴淳,方东,等.复发性口疮流式细胞分析T淋巴细胞亚群.口腔医学,2001,21(1):31- 32.
[27]Gunduz K,Ozturk G,Sozmen EY.Erythrocyte superoxide dismutase,catalase activities and plasma nitrite and nitrate levels in patients with Behcet’s disease and recurrent aphthous stomatitis.Clin Exp Dermatol,2004,29(2):176-9.
[28]Arikan S,Durusoy C,Akalin N,et al.Oxidant/antioxidant status in recurrent aphthous stomatitis.Oral Dis,2009,15(7):512-5.
[29]Momen-Beitollahi J,Mansourian A,Momen-Heravi F,et al.Assessment of salivary and serum antioxidant status in patients with recurrent aphthous stomatitis.Oral Medicine and Pathology,2010,15(4):e557-61.
[30]陈谦明.氧自由基对口腔黏膜损伤的动物实验研究-动物模型的形态和结构变化.华西口腔医学杂志,1993,(1):65-67.
[31]李秉琦.氧自由基对口腔黏膜损伤的动物实验研究-氧自由基对动物黏酶活性的影响.华西口腔医学杂志,1993(2):135-137.
[32]薄芯.生化复合黄腐酸、青黛和绞股蓝总甙对T淋巴细胞转化的影响.中国中医药科技,2003,10(6):351-352.
[33]段炳南,陈庆林.绞股蓝总皂甙对小鼠腹腔巨噬细胞内酶活性及吞噬功能的影响.江西医学院学报,2007,47(3):38-40.
[34]周俐,叶开和,任先达.绞股蓝总苷对免疫功能低下小鼠模型特异性免疫功能的影响.中华中医药学刊,2008,26(1):145-146.
[35]张青蓓,马俊江,曹之宪等.绞股蓝总皂苷对NCTC11637株HP延缓大鼠实验性胃溃疡愈合的治疗作用及其机制.中国药理学通报,1999,15(3):225-228.
[36]王宏涛,叶云,肖顺林等.绞股蓝乙酸乙酯提取物对胃溃疡大鼠胃黏膜血管活性物质的影响.中国中医急症,2008,17(10):1437-1438.
[1]干祖望.干氏耳鼻咽喉口腔科学.南京:江苏科学技术出版社,1990:278-280.
[2]梅武轩.劳绍贤教授从湿热论治复发性口腔溃疡的经验.陕西中医,2006,27(3):322-323.
[3]王跃才,张莲英,普曦娜,等.辨证分型治疗复发性口疮97例报告.云南中医中药杂志,2002, 23(2):30-31.
[4]李翠玉.复发性口疮证治体会.实用中医药杂志,2005,21(4):233.
[5]闫莉莉.活血化瘀方药治疗顽固性口腔溃疡11例.中国民间疗法,2006,14(8):36-37.
[6]李月斌,姜庆荣,王长洲.活血化瘀治疗复发性口腔溃疡33例.山东中医杂志,2003,22(3):153 -154.
[7]过伟峰,周仲瑛,汪红,等.口疮平口服液防治83例复发性口疮复发的临床研究.江苏中医,2002,23(9):9-11.
[8]詹家明,张晓钰.益气清热养阴活血法治疗复发性口腔溃疡30例.上海中医杂志,1998(7):32
[9]薛西林.马骏治疗慢性复发性口腔溃疡的经验.北京中医,2005,24(6):335-336.
[10]陈世友.辨治复发性口腔溃疡56例.中外健康文摘医药月刊, 2006,3(11):99-101.
[11]张军,刘金喜,张萍.辨证分型治疗复发性口腔溃疡46例.陕西中医,2005,26(6):533-534.
[12]程伟,王吉英.辨证治疗复发性口腔溃疡82例.中医药学刊,2005,23(4):744.
[13]王晓山,陈建灵,林茜,等.修疡口服液治疗复发性口疮100例临床研究.甘肃中医,2002,15 (4):24-25.
[14]鞠少斌,李冬莲.清火汤治疗复发性口腔溃疡的临床观察.医学理论与实践杂志,2007,20( 5):564-565.
[15]王红宇.半夏泻心汤化裁治疗复发性口腔溃疡98例.北京中医,2007,26(3):164-165.
[16]成正雄,刘卫平,肖志勇,等.滋阴降火汤治疗复发性口腔溃疡93例疗效观察.长沙医学院学报,2006,16(6):29-32.
[17]姜国平,彭清华,鹿小君.香砂六君子汤加味治疗复发性口腔溃疡40例.江西中医药,2007,( 6):38.
[18]韩燕,贺瀛.加味麦门冬汤治疗阴虚火旺型复发性口腔溃疡60例.中国中西医结合杂志, 2007,27(7):662.
[19]田乃定.黄连阿胶汤治疗复发性口腔溃疡疗效观察.山西中医,2003,19(2):46.
[20]周杰.乌梅丸治疗复发性口腔溃疡.湖北中医杂志,2003,25(8):45.
[21]过伟峰,周仲瑛,汪红,等.口疮平口服液防治72例复发性口疮复发的临床研究.江苏中医, 2002,23(9):9-11.
[22]王晓山,陈建灵,林茜,等.修疡口服液治疗复发性口疮100例临床研究.甘肃中医,2002,15( 4):24-25.
[23]李佩洲,常新华.口疮宁颗粒治疗阴虚火旺型复发性口疮的临床研究.辽宁中医杂志,2002,29(7):411.
[24]黄兆坤.口康饮治疗复发性口腔溃疡的研究.现代中西医结合杂志,2004,13(6):718-719.
[25]孙冰,刘国惠,姚源璋,等.愈溃膜、口宝含片分期治疗复发性口腔溃疡临床研究.山东中医杂志,2000,19(2):74-75.
[26]李彩凤,孙爱英.信青溃疡液治疗复发性口腔溃疡的临床观察.中医药学报,2003,31(6):44- 45.
[27]官纯寿,罗树星.中药喷雾剂治疗复发性口腔溃疡的临床研究.华中科技大学学报,2003,32 (5):558-560.
[28]李丽萍,王海霞,王幼.芪附汤治疗顽固性口腔溃疡45例.现代中西医结合杂志,2007,16( 11):1503.
[29]高洁萱.清肺养阴汤治疗复发性口腔溃疡.山西中医,2007,23(3):75.
[30]刘挺立,迟永利,纪金风,等.二黄汤治疗复发性口腔溃疡临床分析.山东中医药大学学报, 2004,28(3):212-213.
[31]赵敏,刘如霖,李永升.自拟三泰丸治疗复发性口腔溃疡85例.甘肃中医,2000,13(1):30.
[32]陈美南,宋敏,李富玉.自拟清疮汤治疗复发性口腔溃疡临床观察.中医药学刊,2005,23( 12):2297.
[33]苏涛,马旭东.口腔解毒汤治疗复发性阿弗他溃疡临床疗效观察.中国实验方剂学,2010,16 (7).
[34]陈敏,张振贤,吴丽丽,等.芪卿方治疗复发性口腔溃疡临床疗效观察.中国医药指南,2010,8 (6):77-79.
[35]耿平,杨洪凤,岳义国.青茶散治疗复发性口腔溃疡126例.实用中医内科杂志,2003,17(1): 56.
[36]贾文超,任学伟.中西药结合治疗复发性口疮50例.口腔医学,2005,25(4):221.
[37]刘海光,朱斌,张利平.口必健治疗复发性口疮的临床观察.黑龙江医学,2004,28(11):837- 838.
[38]贾泽宇,刘春子,米宏图.中药散剂治疗口腔溃疡的疗效观察.中国社区医师,2007,14(9):79.
[39]孙林琳.复方溃疡散治疗复发性口腔溃疡的疗效观察.口腔医学,2004,24(5):318-319.
[40]王虹,庞彬.芦荟散治疗复发性口疮.湖北中医杂志,2004,26(7):37.
[41]彭楚湘,李元聪.针刺配合中药治疗复发性口腔溃疡86例.湖南中医学院学报,2003,23(2) :51-52.
[42]董杨颖,邓晓莹.中药结合耳针治疗复发性口腔溃疡50例.中国中医药信息杂志,2004,11( 5):437.
[43]陈建灵.谈复发性口疮防治中的难点与对策.辽宁中医学院学报,2005,7(6):602-603.
[44]薛西林.马骏治疗慢性复发性口腔溃疡的经验.北京中医,2005,24(6):335-336.
[45]官纯寿,罗树星.中药喷雾剂治疗复发性口腔溃疡的临床研究.华中科技大学学报,2003,32(5):558-560.
[46]张兰海.雷公藤治疗频发复发性口疮的临床观察.口腔医学,2003,23(1):35-36.
[47]周杰.乌梅丸治疗复发性口腔溃疡30例临床观察.临床口腔医学杂志,2003,19(6):370- 371.
[48]孙林琳.六味地黄丸对复发性口疮患者细胞免疫功能影响的观察.实用口腔医学杂志, 2004,20(5):647-648.
[49]马文斌,步革,谢文忠,等.雷公藤多甙治疗复发性口疮的远期疗效与血清NO及NOS的变化.实用口腔医学杂志,2006,22(2):267-268.
[50]郭红云,刘秀玉.中药治疗复发性阿弗他溃疡免疫调节与疗效观察.中国民康医学,2006,18(6):434-435.
[51]王淑慧,严长宏.蒲黄一物散治疗阿弗他性口炎70例.新中医,2007,39(3):69-70.
[52]朱金晓,单莉英,刘志辉,等.黄芪治疗复发性阿弗他溃疡疗效分析及作用机理探讨.临床口腔医学杂志,2007,23(11):668-671.
[53]胡渝芳,张永忠.甘草泻心汤治疗复发性阿弗他溃疡的T淋巴细胞亚群变化.实用药物与临床,2008,11(2):68-69.
[54]朱康伟.贞芪扶正颗粒治疗复发性口疮52例.中医中药,2009,47(18):136-139.