补肾明目口服液联合糖皮质激素体外对慢性葡萄膜炎患者外周血淋巴细胞凋亡率及Fas和FasL表达的影响
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摘要
目的
研究补肾明目口服液对慢性葡萄膜炎患者外周血淋巴细胞凋亡和Fas、FasL表达活性的影响,探讨补肾明目口服液在葡萄膜炎慢性化发病机制中的干预作用。
方法
采用血清药理学方法,制取补肾明目口服液含药兔血清。运用流式细胞仪检测8例慢性葡萄膜炎患者外周血淋巴细胞在不同浓度的补肾明目口服液的含药血清(20%,10%,5%)、地塞米松(0.001 mol／L)及两者联合刺激下淋巴细胞凋亡和Fas,FasL表达的变化。
结果
①慢性葡萄膜炎患者PBL凋亡率低于正常组(P<0.05),Fas表达高于正常组(P<0.05),FasL表达与正常组差异不明显(P>0.05)；②10%,20%含药血清可增加慢性葡萄膜炎患者PBL的凋亡率(P<0.01),降低Fas表达(P<0.01),升高FasL的阳性细胞率(P<0.01)；③地塞米松可增高慢性葡萄膜炎患者PBL的凋亡率(P<0.01),对比含药血清组明显提高(P<0.01)；④含药血清联合地塞米松可以显著增加PBL凋亡率(P<0.01),降低Fas表达(P<0.05),升高FasL的阳性细胞率(P<0.01)。
结论
慢性葡萄膜炎患者PBL存在凋亡及凋亡相关蛋白表达的紊乱,中药补肾明目口服液在体外可纠正其紊乱,增高PBL的凋亡。为中药延缓慢性葡萄膜炎复发提供了理论基础。
Purpose
Research on the effect of Bushenmingmu oral solution which activied on peripheral lymphocyte apoptosis and Fas, FasL expression in patients with chronic uveitis. Discuss on the intervention role of Bushenmingmu in chronic uveitis pathogenesis.
Methods
Using serumal pharmacological method of making rabbit serum which contains Bushenmingmu oral. The use of flow cytemetry to detective apoptosis and Fas, FasL expressions on 8 cases of chronic uveitis in patients with peripheral blood lymphocytes in different concentrations of Bushenmingmu oral serum (20%,10%,5%), dexamethasone (0.001 mol/L) and both the united stimulated.
Results
①patients with chronic uveitis PBL apoptosis rate was lower than the normal group (P<0.05), Fas expression was more than the normal group (P<0.01), FasL expression shows nonsignificant differences (P>0.05);②10%,20%serum shows the increasing on rate of PBL apoptosis in patients with chronic uveitis (P<0.01), a significant reduction in Fas expression ((P<0.01), an increased rate of FasL-positive cells (P<0.01);③dexamethasone could increase the rate of PBL apoptosis in patients with chronic uveitis (P<0.01), and has a significant increasing when compare the to the serum group (P<0.01);④serum combined with dexamethasone can significantly increase PBL apoptosis rate (P<0.01), lower Fas expression (P<0.05), significantly higher rates of FasL positive cells (P<0.01).
Conclusions
PBL in patients with chronic uveitis exist the apoptosis and apoptosis-related protein expression disorders, bushenmingmu oral solution in vitro could correct their disorders, and increase PBL apoptosis.It also provides a theoretical foundation on Chinese traditional medicine delayed relapse of chronic uveitis.
研究补肾明目口服液对慢性葡萄膜炎患者外周血淋巴细胞凋亡和Fas、FasL表达活性的影响,探讨补肾明目口服液在葡萄膜炎慢性化发病机制中的干预作用。
方法
采用血清药理学方法,制取补肾明目口服液含药兔血清。运用流式细胞仪检测8例慢性葡萄膜炎患者外周血淋巴细胞在不同浓度的补肾明目口服液的含药血清(20%,10%,5%)、地塞米松(0.001 mol／L)及两者联合刺激下淋巴细胞凋亡和Fas,FasL表达的变化。
结果
①慢性葡萄膜炎患者PBL凋亡率低于正常组(P<0.05),Fas表达高于正常组(P<0.05),FasL表达与正常组差异不明显(P>0.05)；②10%,20%含药血清可增加慢性葡萄膜炎患者PBL的凋亡率(P<0.01),降低Fas表达(P<0.01),升高FasL的阳性细胞率(P<0.01)；③地塞米松可增高慢性葡萄膜炎患者PBL的凋亡率(P<0.01),对比含药血清组明显提高(P<0.01)；④含药血清联合地塞米松可以显著增加PBL凋亡率(P<0.01),降低Fas表达(P<0.05),升高FasL的阳性细胞率(P<0.01)。
结论
慢性葡萄膜炎患者PBL存在凋亡及凋亡相关蛋白表达的紊乱,中药补肾明目口服液在体外可纠正其紊乱,增高PBL的凋亡。为中药延缓慢性葡萄膜炎复发提供了理论基础。
Purpose
Research on the effect of Bushenmingmu oral solution which activied on peripheral lymphocyte apoptosis and Fas, FasL expression in patients with chronic uveitis. Discuss on the intervention role of Bushenmingmu in chronic uveitis pathogenesis.
Methods
Using serumal pharmacological method of making rabbit serum which contains Bushenmingmu oral. The use of flow cytemetry to detective apoptosis and Fas, FasL expressions on 8 cases of chronic uveitis in patients with peripheral blood lymphocytes in different concentrations of Bushenmingmu oral serum (20%,10%,5%), dexamethasone (0.001 mol/L) and both the united stimulated.
Results
①patients with chronic uveitis PBL apoptosis rate was lower than the normal group (P<0.05), Fas expression was more than the normal group (P<0.01), FasL expression shows nonsignificant differences (P>0.05);②10%,20%serum shows the increasing on rate of PBL apoptosis in patients with chronic uveitis (P<0.01), a significant reduction in Fas expression ((P<0.01), an increased rate of FasL-positive cells (P<0.01);③dexamethasone could increase the rate of PBL apoptosis in patients with chronic uveitis (P<0.01), and has a significant increasing when compare the to the serum group (P<0.01);④serum combined with dexamethasone can significantly increase PBL apoptosis rate (P<0.01), lower Fas expression (P<0.05), significantly higher rates of FasL positive cells (P<0.01).
Conclusions
PBL in patients with chronic uveitis exist the apoptosis and apoptosis-related protein expression disorders, bushenmingmu oral solution in vitro could correct their disorders, and increase PBL apoptosis.It also provides a theoretical foundation on Chinese traditional medicine delayed relapse of chronic uveitis.
引文
[1]杨培增.临床葡萄膜炎[M].北京：人民卫生出版社,2004.43-44.
[2]杨培增,邢琳.我国近五年葡萄膜炎临床与基础研究进展[J].中华眼科杂志,2005,41(8)：743-747.
[3]刘静霞,陈大颖.葡萄膜炎的中西医防治研究[J].中华现代眼耳鼻喉科杂志,2007,4(4)：313-315.
[4]Yang P, Ji L, Zhou H, et al. Disturbed expression of Fas/FasL on c and c T cells in Behcets disease, Vogt—Koyanagi—Harada syndrome and Idiopathic anterior uveitis. Ocul-Immunology andInflammation,2001,9: 185-191.
[5]陈玲,杨培增,周红颜,等.伏格特—小柳—原田综合征患者外周血淋巴细胞Fas和FasL mRNA的表达[J].中华眼科杂志,2004,40：507-509.
[6]Yang P, Chen L, Zhou H, et al. Resistance of lymphocytes to Fas —mediated apoptosis in Behcets disease and Vogt—Koyanagi—Harada syndrome. Ocul Immunol Inflamm,2002,10:47-52.
[7]ChanCC, MattesonDM, Li Q, etal. Arch Ophthalmol,1997,115:1559
[8]崔晓兰,贺玉琢,高英杰.中药药理研究的新思路——中药血清药理学[J].中国中医药科技,1997,4(4)：239-250.
[9]高月,等.中药复方物质基础的研究[J].中国新药杂志,2000.05.15,9(5)：307-308.
[10]章淑华.陆绵绵治疗葡萄膜炎的经验[J].湖北中医杂志,2000,22(6)：3-4.
[11]姚芳蔚.葡萄膜炎辨证施治[J].中西医结合眼科杂志,1997,15(3)：129—131.
[12]曾庆华.中医眼科学[M].北京：中国中医药出版社,2007.177-178.
[13]邵愚.瞳神紧小的古文献证治概要[J].辽宁中医药大学学报,2006.11,8(6).
[14]颜廷芹,郭霞.中医药延长葡萄膜炎复发间隔时间作用机制[J].山东中医药大学学报,2006.09,30(5)：365-367.
[15]詹宇坚,付志慧.葡萄膜炎的中医治疗研究近况[J].中国中医眼科杂志,1996,6(1)：61—63.
[16]李金田.通窍活血汤治疗眼科急症举隅[J].北京中医学院学报,1991.14(4)：15-16.
[17]罗国芬.陈达夫中医眼科临床经验[M].四川科技出版社,1985：47.
[18]杨培增.葡萄膜炎的研究进展[J].中华眼科杂志,2005.12,41(12)：1149-1152.
[19]Yang PZ, Herzberg NH, Zhou HY, et al. Apoptosis of infiltrating cells in experimental autoimmune uveoretinitis. Chin Med J,2000,113:643-646.
[20]Yang P, Justine R, Smith K, etal. Visualization of cell death invivo duringmurine endotoxin- induced uveitis. Invest Ophthalmol VisSci,2003, 44:1993-1997.
[21]褚利群,杨培增,李兵,等.实验性自身免疫性葡萄膜视网膜炎中T-bet的表达及意义[J].中华眼底病杂志,2004,20：172-174.
[22]Li B, Yang P, Zhou H, et al. T-bet expression is upregulated inactive Behcet's disease. Br J Ophthalmol,2003.87:1264-1267.
[23]杨培增,钟华红,周红颜,等.人眼组织中共刺激分子、Fas/FasL及主要组织相溶性复合体Ⅱ类分子的免疫组织化学研究[J].中华眼底病杂志,2003,19：109-112.
[24]王红,杨培增,张震,等.Behcet's病患者外周血淋巴细胞共刺激分子的表达[J].中华眼底病杂志,2003.19：357-359.
[25]邢琳,杨培增,陈璇,等.实验性自身免疫性葡萄膜视网膜炎中可诱导的共刺激分子的表达及意义[J].中华眼底病杂志,2005,21：114-117.
[26]丁海明,吕厚山,蒋东芳,等.HLA-B2704转基因小鼠自发性前葡萄膜炎[J].中华风湿病学杂志,2000,4：199-201
[27]杨培增.临床葡萄膜炎[M].北京人民卫生出版社,2004.33-178,107-210.
[28]杨培增,王红,周红颜,等.Vogt-Koyanagi-Harada综合征的治疗[J].中华眼科杂志,2002,38：196-199.
[29]张美芬,刘勤,闵寒毅,等.Vogt-Koyanagi-Harada综合征的治疗与预后[J]. 中华眼科杂志,2002,38：200-203.
[30]Smith JR, Rosenbaum JT. Management of uveitis:arheumatologic perspective. Arthritis Rheum,2002,46:309-318.
[31]Foster CS. General principles and philosophy. In:Foster CS, VitalAT, eds. Diagnosis and treatment of uveitis. Philadelphia:WBSaunders, 2002,27-33.
[32]Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol,2003, 87:24-27.
[33]Foster CS, Vitale AT. Immuno suppressive chemotherapy. In:Foster CS, Vital AT, eds. Diagnosis and treatment of uveitis. Philadelphia:WB Saunders,2002.177-214.
[34]K°tter I, Zierhut M, Eckstein AK, etal. Human recombinant interferon alfa22a for the treatment of Behcet's disease with sight threatening posterior or panuveitis. Br J Ophthalmol,2003,87:423-431.
[35]曹宪勇,张振霞,李梅英.雷公藤与干扰素在治疗葡萄膜炎中的应用[J].眼科新进展,1995,15(1)：25-26.
[36]肖继皋,吴树杨,王育良.汉防己甲素对实验性葡萄膜炎的治疗作用及机制[J].中华眼底病杂志,1994,10：1491.
[37]周婉瑜,李越虹,麻柔,等.中药明目汤对白塞氏病葡萄膜炎患者T淋巴细胞亚群的影响[J].中国中西医结合杂志.2002.09,22(9).
[38]崔晓兰,贺玉琢,高英杰.中药药理研究的新思路——中药血清药理学[J].中国中医药科技,1997,4(4)：239-250.
[39]叶庆忠,许云禄.血清药理学的研究进展[J].海峡药学,2006.18(4)：8-11.
[40]詹红生,石印玉,赵咏芳,等.补肾复方载药血清对骨吸收陷窝影响的时效关系研究[J].浙江中医学院学报,2001,25(2)：21-22.
[41]王国佐.血清药理学方法在中药研究中的进展[J].湖南中医药大学学报.2007.06,27(3)：78-80.
[42]樊亚萱,文爱东,黄熙,等.正常及急性局部血瘀证犬动物模型静脉注射四甲 基毗嗪的药动学[J].第四军医太学学报,1995,16(6)：479-480.
[43]李仪奎,吴建宇.血清药理学实验中采血时间的通法方案[J].中国药理学通报,1999,15(6)：569-570.
[44]程志安,吴燕峰,曾志勇,等.健骨二仙丸载药血清对人成骨细胞增殖及细胞周期的影响[J].中国中西医结合杂志,2002,22(2)：129-132
[45]马涛,崔燎,吴铁,等.老年大鼠含淫羊藿血清对成骨细胞的增殖与分化的影响[J].中国骨质疏松杂志,2002,8(1)：55-57.
[46]冯伟,石印玉,沈培芝,等.MTT法分析中药载药血清对体外软骨细胞增殖影响的研究[J].上海中医药大学学报,2000,14(1)：43-45.
[47]包云,王灵台.高效液相色谱法在抗纤复方药物血清质量控制中的应用研究[J].江苏临床医学杂志,2000,4(4)：266-268.
[48]UmedaM, Amagaya S, Ogihara Y, et al. Effets of certain herbal medicine on thebiotransformation of arachidonic acid:A new pharmacological testing method using serum. J Enthnopharmacol,1988,23:91-98.
[49]李仪奎.中药血清药理学实验方法的若干问题[J].中药新药与临床药理,1999,9(2)：95-98.
[50]王宁生,雷燕,刘平,等.关于中药血清药理学的若干思考[J].中国中西医结合杂志,1999,19(5)：263-266
[51]詹红生,赵咏芳,石印玉,等.用载药血清方法观察补肾益精方对破骨细胞功能的影响[J].中国骨伤,2001,14(3)：145-147.
[52]阴赤贞宏,李兰芳,金亚宏,等.当归补血汤载药血清对小鼠白细胞的活化作用[J].中国中医药科技,1999,6(1)：19-21.
[53]徐瑶,卞国武,吴敏琉.淫羊藿醇提取物对内皮细胞释放NO的影响[J].中药新药与临床药理,2001,12(1)：38-40.
[54]周明眉,杨奎,姜远平,等.中药血清药理学的方法学研究-含药血清低温保存和血清灭活的影响[J].中药药理与临床,1999,15(2)：44-46
[55]徐海波,吴清和.中药血清药理学实验方法的探讨[J].中国中医药科技,2000,7(1)：43
[56]崔玲,晏卫东.中药血清药理研究方法回顾与展望[J].武警医 学,2004,15(6)：460-461。
[57]贺石林,葛金文.质疑血清药理学,加强多层次半体内实验研究[J].中国药理学通报,2005,21(3)：277-279.
[58]Yonehara S, Ishii A,Yonehara M. JExp Med,1989,169:1747.
[59]Dhein J, Daniel PT, Trauth BC, etal.J Immunol,1992,149:3166.
[60]Suda T, Takahashi T,Golstein P,etal. Cell,1993,75:1169.
[61]Ju SR, Fanka CJ, Rothstein A. Fas (CD95)/FasL interacttions required for program-med cell death after T cell activetion[J]. Nature,1995; 373 (6513):444-446.
[62]Kummer S. ZCE-like proteases in apoptosis [J]. Trends Biochem Sci, 1995; 20:198-201.
[63]Oshimi Y, Miyazki S. J Immunol,1995,154:599.
[64]O'Connell J, MichaelW, BennettMW, et al. Fas resistance and counter attack in the tumor-immune conflict [J]. Ann NY Acad Sci,2000; 910:178.
[65]杨培增,Herzbery NH,周红颜,等.实验性自身免疫性葡萄膜炎组织切片研究[J].中华眼底病杂志,2000；16：35.
[66]Nakamura S,Sugita M, Matoba H,etal.Insufficient expression of Fas antigen on helper T cells in Behcet's disease[J]. Br J Ophthalmol 1996; 80:174-176.
[67]Nakamura S, SugitaM, IgaiQ, etal. Fas genes transfer on helper T cells in Behcet's disease[J]. B r J Ophthalmol,1997; 101:975.
[68]OhtaK,YoshimuraN.Graefe'sArchClinExp Ophthalmol1998,236: 434.
[69]籍莉,杨培增,孔庆瑜,等.Fas/Fasl抗原在葡萄膜炎患者外周血T淋巴细胞上的表达[J].眼视光学杂志.2001.3(4).
[70]陈玲,杨培增,周红颜,等.伏格特-小柳-原田综合征患者外周血淋巴细胞Fas和Fasl mRNA的表达[J].中华眼科杂志.2004.08,40(8).
[71]庄唯,高清平.地塞米松、环孢素A对慢性特发性血小板减少性紫癜患者淋巴细胞凋亡的影响[J].临床内科杂志,2009.01,26(1)：41-43.
[72]Tomoyasu Yoshinol, Hiroyuki Kishil, Takuya Nagatal, et al. Diferential involvement of p38 MAP kinase pathway an d Bax.transloeation in the mitochondria.mediated cell death in TCR. and dexamethasone. stimula ted thymocytes. Eur J Immunol,2001,31:2702-2708.
[73]Maria Cfistina Marehetti, Barbara Di Marco, Mafia Cristina Santini, etal. Dexamethasone—induced thymocytes apoptosis requires glucocortieoidreceptor nuclear translocation but not rnitochondrlal membrane potentialtransition. Toxicology Lettem,2003,139:175—180.
[74]Salvioli S,Barbi C, Dobrueki J, el al. Opposite role of changes in mitochondfial membrane potential in diferent apo ptotic processes. FEBS Letters,2000,469:186-190.
[75]Irazuzta J, Pretzaf RK, Zingarelli B. Caspases inhibition decreases neurological sequelae in meningitis. Critical Care Medicine,2008,36: 1603-1606.
【1】 Boise LH, Thompson CB. Hierarchical control of lymphocyte survival[J].Science,1996,274(5284):67-68.
【2】 Yonehara S, Ishii A,Yonehara M. J Exp Med,1989,169:1747
【3】 Dhein J,Daniel PT,Trauth BC,et al. J Immunol,1992,149:3166
【4】 Suda T,Takahashi T,Golstein P,et al. Cell,1993,75:1169
【5】 Ju SR, Fanka CJ, Rothstein A. Fas (CD95)/Fasl interacttions required for program-med cell death after T cell activetion[J]. Nature,1995; 373 (6513):444-446
[6]杨培增,周红颜葡萄膜炎基础研究的新进展-第四届国际葡萄膜炎大会纪要,国外医学眼科学分册,1998年,第22卷,第4期：193-196
[7]桑威,Fas/Fasl系统参与的几种生物学效应,国际免疫学杂志2006年11月第29卷第6期
【8】 Plumas J,Chaperot L,Richard MJ,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19(9):1597-1604.
【9】 O'Connell J,MichaelW, BennettMW, et al. Fas resistance and counter attack in the tumor-immune conflict [J]. Ann NY Acad Sci,2000; 910:178
[10]杨培增,Herzbery NH,周红颜,等,实验性自身免疫性葡萄膜炎组织切片研究,[J].中华眼底病杂志,2000；16：35
【11】 Chan CC,Matteson DM,L iQ, et al. Regulation of Fas and Fas ligand expression in T cell [J].Arch Ophthalmol,1997; 115:1559
[12]Nakamura S, Sugita M,Matoba H, et al. Insufficient expression of Fas antigen on helper T cells in Behcet's disease[J]. Br J Ophthalmol 1996; 80:174-176
[13]Nakamura S, SugitaM, IgaiQ, et al. Fas genes transfer on helper T cells in Behcet's disease[J]. B r J Ophthalmol,1997; 101:975
[14]OhtaK,YoshimuraN.Graefe'sArchClinExp Ophthalmol 1998,236:434
[15]籍莉,杨培增,孔庆瑜,周红颜,林健贤,刘平,黄祥坤,谢楚芳,Fas／Fasl抗原在葡萄膜炎患者外周血T淋巴细胞上的表达,眼视光学杂志,2001年,第三卷,第四期。
[16]陈玲,杨培增,周红颜,黄祥坤,钟晖,谢楚芳,伏格特-小柳-原田综合征患者外周血淋巴细胞Fas和Fasl mRNA的表达,中华眼科杂志,2004年8月第40卷第8期。
[17]Yang P, Ji L, Zhou H, et al. Disturbed expression of Fas/Fasl on CD4 (+) and CD8 (+) T cells in Behcet's disease, Vogt-Koyanagi-Harada syndrome and idiopathic anterior uveitis. Ocul Immunol and Inflamm,2001,9:185-191.
[18]Yang P, Chen L, Zhou H, et al. Resistance of lymphocytes to Fas-mediated apoptosis in Behcet's disease and Vogt-Koyanagi-Harada syndrome. Ocul Immuno 1 and Inflamm,2002,10: 47252.
[19]曹宪勇,张振霞,李梅英,雷公藤与干扰素在治疗葡萄膜炎中的应用,[J]1眼科新进展,1995,15(1)：25-261
[20]肖继皋,吴树杨,王育良,汉防己甲素对实验性葡萄膜炎的治疗作用及机制,[J]1中华眼底病杂志,1994,10：1491
[19-20]宋艳,詹宇坚,古继红,葡萄膜炎与相关细胞因子的研究进展,中国中医眼科杂志2004年8月第14卷第3期
[21]周婉瑜,李越虹,麻柔,许勇钢,中药明目汤对白塞氏病葡萄膜炎患者T淋巴细胞亚群的影响,中国中西医结合杂志2002年9月第22卷第9期
[2]杨培增,邢琳.我国近五年葡萄膜炎临床与基础研究进展[J].中华眼科杂志,2005,41(8)：743-747.
[3]刘静霞,陈大颖.葡萄膜炎的中西医防治研究[J].中华现代眼耳鼻喉科杂志,2007,4(4)：313-315.
[4]Yang P, Ji L, Zhou H, et al. Disturbed expression of Fas/FasL on c and c T cells in Behcets disease, Vogt—Koyanagi—Harada syndrome and Idiopathic anterior uveitis. Ocul-Immunology andInflammation,2001,9: 185-191.
[5]陈玲,杨培增,周红颜,等.伏格特—小柳—原田综合征患者外周血淋巴细胞Fas和FasL mRNA的表达[J].中华眼科杂志,2004,40：507-509.
[6]Yang P, Chen L, Zhou H, et al. Resistance of lymphocytes to Fas —mediated apoptosis in Behcets disease and Vogt—Koyanagi—Harada syndrome. Ocul Immunol Inflamm,2002,10:47-52.
[7]ChanCC, MattesonDM, Li Q, etal. Arch Ophthalmol,1997,115:1559
[8]崔晓兰,贺玉琢,高英杰.中药药理研究的新思路——中药血清药理学[J].中国中医药科技,1997,4(4)：239-250.
[9]高月,等.中药复方物质基础的研究[J].中国新药杂志,2000.05.15,9(5)：307-308.
[10]章淑华.陆绵绵治疗葡萄膜炎的经验[J].湖北中医杂志,2000,22(6)：3-4.
[11]姚芳蔚.葡萄膜炎辨证施治[J].中西医结合眼科杂志,1997,15(3)：129—131.
[12]曾庆华.中医眼科学[M].北京：中国中医药出版社,2007.177-178.
[13]邵愚.瞳神紧小的古文献证治概要[J].辽宁中医药大学学报,2006.11,8(6).
[14]颜廷芹,郭霞.中医药延长葡萄膜炎复发间隔时间作用机制[J].山东中医药大学学报,2006.09,30(5)：365-367.
[15]詹宇坚,付志慧.葡萄膜炎的中医治疗研究近况[J].中国中医眼科杂志,1996,6(1)：61—63.
[16]李金田.通窍活血汤治疗眼科急症举隅[J].北京中医学院学报,1991.14(4)：15-16.
[17]罗国芬.陈达夫中医眼科临床经验[M].四川科技出版社,1985：47.
[18]杨培增.葡萄膜炎的研究进展[J].中华眼科杂志,2005.12,41(12)：1149-1152.
[19]Yang PZ, Herzberg NH, Zhou HY, et al. Apoptosis of infiltrating cells in experimental autoimmune uveoretinitis. Chin Med J,2000,113:643-646.
[20]Yang P, Justine R, Smith K, etal. Visualization of cell death invivo duringmurine endotoxin- induced uveitis. Invest Ophthalmol VisSci,2003, 44:1993-1997.
[21]褚利群,杨培增,李兵,等.实验性自身免疫性葡萄膜视网膜炎中T-bet的表达及意义[J].中华眼底病杂志,2004,20：172-174.
[22]Li B, Yang P, Zhou H, et al. T-bet expression is upregulated inactive Behcet's disease. Br J Ophthalmol,2003.87:1264-1267.
[23]杨培增,钟华红,周红颜,等.人眼组织中共刺激分子、Fas/FasL及主要组织相溶性复合体Ⅱ类分子的免疫组织化学研究[J].中华眼底病杂志,2003,19：109-112.
[24]王红,杨培增,张震,等.Behcet's病患者外周血淋巴细胞共刺激分子的表达[J].中华眼底病杂志,2003.19：357-359.
[25]邢琳,杨培增,陈璇,等.实验性自身免疫性葡萄膜视网膜炎中可诱导的共刺激分子的表达及意义[J].中华眼底病杂志,2005,21：114-117.
[26]丁海明,吕厚山,蒋东芳,等.HLA-B2704转基因小鼠自发性前葡萄膜炎[J].中华风湿病学杂志,2000,4：199-201
[27]杨培增.临床葡萄膜炎[M].北京人民卫生出版社,2004.33-178,107-210.
[28]杨培增,王红,周红颜,等.Vogt-Koyanagi-Harada综合征的治疗[J].中华眼科杂志,2002,38：196-199.
[29]张美芬,刘勤,闵寒毅,等.Vogt-Koyanagi-Harada综合征的治疗与预后[J]. 中华眼科杂志,2002,38：200-203.
[30]Smith JR, Rosenbaum JT. Management of uveitis:arheumatologic perspective. Arthritis Rheum,2002,46:309-318.
[31]Foster CS. General principles and philosophy. In:Foster CS, VitalAT, eds. Diagnosis and treatment of uveitis. Philadelphia:WBSaunders, 2002,27-33.
[32]Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol,2003, 87:24-27.
[33]Foster CS, Vitale AT. Immuno suppressive chemotherapy. In:Foster CS, Vital AT, eds. Diagnosis and treatment of uveitis. Philadelphia:WB Saunders,2002.177-214.
[34]K°tter I, Zierhut M, Eckstein AK, etal. Human recombinant interferon alfa22a for the treatment of Behcet's disease with sight threatening posterior or panuveitis. Br J Ophthalmol,2003,87:423-431.
[35]曹宪勇,张振霞,李梅英.雷公藤与干扰素在治疗葡萄膜炎中的应用[J].眼科新进展,1995,15(1)：25-26.
[36]肖继皋,吴树杨,王育良.汉防己甲素对实验性葡萄膜炎的治疗作用及机制[J].中华眼底病杂志,1994,10：1491.
[37]周婉瑜,李越虹,麻柔,等.中药明目汤对白塞氏病葡萄膜炎患者T淋巴细胞亚群的影响[J].中国中西医结合杂志.2002.09,22(9).
[38]崔晓兰,贺玉琢,高英杰.中药药理研究的新思路——中药血清药理学[J].中国中医药科技,1997,4(4)：239-250.
[39]叶庆忠,许云禄.血清药理学的研究进展[J].海峡药学,2006.18(4)：8-11.
[40]詹红生,石印玉,赵咏芳,等.补肾复方载药血清对骨吸收陷窝影响的时效关系研究[J].浙江中医学院学报,2001,25(2)：21-22.
[41]王国佐.血清药理学方法在中药研究中的进展[J].湖南中医药大学学报.2007.06,27(3)：78-80.
[42]樊亚萱,文爱东,黄熙,等.正常及急性局部血瘀证犬动物模型静脉注射四甲 基毗嗪的药动学[J].第四军医太学学报,1995,16(6)：479-480.
[43]李仪奎,吴建宇.血清药理学实验中采血时间的通法方案[J].中国药理学通报,1999,15(6)：569-570.
[44]程志安,吴燕峰,曾志勇,等.健骨二仙丸载药血清对人成骨细胞增殖及细胞周期的影响[J].中国中西医结合杂志,2002,22(2)：129-132
[45]马涛,崔燎,吴铁,等.老年大鼠含淫羊藿血清对成骨细胞的增殖与分化的影响[J].中国骨质疏松杂志,2002,8(1)：55-57.
[46]冯伟,石印玉,沈培芝,等.MTT法分析中药载药血清对体外软骨细胞增殖影响的研究[J].上海中医药大学学报,2000,14(1)：43-45.
[47]包云,王灵台.高效液相色谱法在抗纤复方药物血清质量控制中的应用研究[J].江苏临床医学杂志,2000,4(4)：266-268.
[48]UmedaM, Amagaya S, Ogihara Y, et al. Effets of certain herbal medicine on thebiotransformation of arachidonic acid:A new pharmacological testing method using serum. J Enthnopharmacol,1988,23:91-98.
[49]李仪奎.中药血清药理学实验方法的若干问题[J].中药新药与临床药理,1999,9(2)：95-98.
[50]王宁生,雷燕,刘平,等.关于中药血清药理学的若干思考[J].中国中西医结合杂志,1999,19(5)：263-266
[51]詹红生,赵咏芳,石印玉,等.用载药血清方法观察补肾益精方对破骨细胞功能的影响[J].中国骨伤,2001,14(3)：145-147.
[52]阴赤贞宏,李兰芳,金亚宏,等.当归补血汤载药血清对小鼠白细胞的活化作用[J].中国中医药科技,1999,6(1)：19-21.
[53]徐瑶,卞国武,吴敏琉.淫羊藿醇提取物对内皮细胞释放NO的影响[J].中药新药与临床药理,2001,12(1)：38-40.
[54]周明眉,杨奎,姜远平,等.中药血清药理学的方法学研究-含药血清低温保存和血清灭活的影响[J].中药药理与临床,1999,15(2)：44-46
[55]徐海波,吴清和.中药血清药理学实验方法的探讨[J].中国中医药科技,2000,7(1)：43
[56]崔玲,晏卫东.中药血清药理研究方法回顾与展望[J].武警医 学,2004,15(6)：460-461。
[57]贺石林,葛金文.质疑血清药理学,加强多层次半体内实验研究[J].中国药理学通报,2005,21(3)：277-279.
[58]Yonehara S, Ishii A,Yonehara M. JExp Med,1989,169:1747.
[59]Dhein J, Daniel PT, Trauth BC, etal.J Immunol,1992,149:3166.
[60]Suda T, Takahashi T,Golstein P,etal. Cell,1993,75:1169.
[61]Ju SR, Fanka CJ, Rothstein A. Fas (CD95)/FasL interacttions required for program-med cell death after T cell activetion[J]. Nature,1995; 373 (6513):444-446.
[62]Kummer S. ZCE-like proteases in apoptosis [J]. Trends Biochem Sci, 1995; 20:198-201.
[63]Oshimi Y, Miyazki S. J Immunol,1995,154:599.
[64]O'Connell J, MichaelW, BennettMW, et al. Fas resistance and counter attack in the tumor-immune conflict [J]. Ann NY Acad Sci,2000; 910:178.
[65]杨培增,Herzbery NH,周红颜,等.实验性自身免疫性葡萄膜炎组织切片研究[J].中华眼底病杂志,2000；16：35.
[66]Nakamura S,Sugita M, Matoba H,etal.Insufficient expression of Fas antigen on helper T cells in Behcet's disease[J]. Br J Ophthalmol 1996; 80:174-176.
[67]Nakamura S, SugitaM, IgaiQ, etal. Fas genes transfer on helper T cells in Behcet's disease[J]. B r J Ophthalmol,1997; 101:975.
[68]OhtaK,YoshimuraN.Graefe'sArchClinExp Ophthalmol1998,236: 434.
[69]籍莉,杨培增,孔庆瑜,等.Fas/Fasl抗原在葡萄膜炎患者外周血T淋巴细胞上的表达[J].眼视光学杂志.2001.3(4).
[70]陈玲,杨培增,周红颜,等.伏格特-小柳-原田综合征患者外周血淋巴细胞Fas和Fasl mRNA的表达[J].中华眼科杂志.2004.08,40(8).
[71]庄唯,高清平.地塞米松、环孢素A对慢性特发性血小板减少性紫癜患者淋巴细胞凋亡的影响[J].临床内科杂志,2009.01,26(1)：41-43.
[72]Tomoyasu Yoshinol, Hiroyuki Kishil, Takuya Nagatal, et al. Diferential involvement of p38 MAP kinase pathway an d Bax.transloeation in the mitochondria.mediated cell death in TCR. and dexamethasone. stimula ted thymocytes. Eur J Immunol,2001,31:2702-2708.
[73]Maria Cfistina Marehetti, Barbara Di Marco, Mafia Cristina Santini, etal. Dexamethasone—induced thymocytes apoptosis requires glucocortieoidreceptor nuclear translocation but not rnitochondrlal membrane potentialtransition. Toxicology Lettem,2003,139:175—180.
[74]Salvioli S,Barbi C, Dobrueki J, el al. Opposite role of changes in mitochondfial membrane potential in diferent apo ptotic processes. FEBS Letters,2000,469:186-190.
[75]Irazuzta J, Pretzaf RK, Zingarelli B. Caspases inhibition decreases neurological sequelae in meningitis. Critical Care Medicine,2008,36: 1603-1606.
【1】 Boise LH, Thompson CB. Hierarchical control of lymphocyte survival[J].Science,1996,274(5284):67-68.
【2】 Yonehara S, Ishii A,Yonehara M. J Exp Med,1989,169:1747
【3】 Dhein J,Daniel PT,Trauth BC,et al. J Immunol,1992,149:3166
【4】 Suda T,Takahashi T,Golstein P,et al. Cell,1993,75:1169
【5】 Ju SR, Fanka CJ, Rothstein A. Fas (CD95)/Fasl interacttions required for program-med cell death after T cell activetion[J]. Nature,1995; 373 (6513):444-446
[6]杨培增,周红颜葡萄膜炎基础研究的新进展-第四届国际葡萄膜炎大会纪要,国外医学眼科学分册,1998年,第22卷,第4期：193-196
[7]桑威,Fas/Fasl系统参与的几种生物学效应,国际免疫学杂志2006年11月第29卷第6期
【8】 Plumas J,Chaperot L,Richard MJ,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19(9):1597-1604.
【9】 O'Connell J,MichaelW, BennettMW, et al. Fas resistance and counter attack in the tumor-immune conflict [J]. Ann NY Acad Sci,2000; 910:178
[10]杨培增,Herzbery NH,周红颜,等,实验性自身免疫性葡萄膜炎组织切片研究,[J].中华眼底病杂志,2000；16：35
【11】 Chan CC,Matteson DM,L iQ, et al. Regulation of Fas and Fas ligand expression in T cell [J].Arch Ophthalmol,1997; 115:1559
[12]Nakamura S, Sugita M,Matoba H, et al. Insufficient expression of Fas antigen on helper T cells in Behcet's disease[J]. Br J Ophthalmol 1996; 80:174-176
[13]Nakamura S, SugitaM, IgaiQ, et al. Fas genes transfer on helper T cells in Behcet's disease[J]. B r J Ophthalmol,1997; 101:975
[14]OhtaK,YoshimuraN.Graefe'sArchClinExp Ophthalmol 1998,236:434
[15]籍莉,杨培增,孔庆瑜,周红颜,林健贤,刘平,黄祥坤,谢楚芳,Fas／Fasl抗原在葡萄膜炎患者外周血T淋巴细胞上的表达,眼视光学杂志,2001年,第三卷,第四期。
[16]陈玲,杨培增,周红颜,黄祥坤,钟晖,谢楚芳,伏格特-小柳-原田综合征患者外周血淋巴细胞Fas和Fasl mRNA的表达,中华眼科杂志,2004年8月第40卷第8期。
[17]Yang P, Ji L, Zhou H, et al. Disturbed expression of Fas/Fasl on CD4 (+) and CD8 (+) T cells in Behcet's disease, Vogt-Koyanagi-Harada syndrome and idiopathic anterior uveitis. Ocul Immunol and Inflamm,2001,9:185-191.
[18]Yang P, Chen L, Zhou H, et al. Resistance of lymphocytes to Fas-mediated apoptosis in Behcet's disease and Vogt-Koyanagi-Harada syndrome. Ocul Immuno 1 and Inflamm,2002,10: 47252.
[19]曹宪勇,张振霞,李梅英,雷公藤与干扰素在治疗葡萄膜炎中的应用,[J]1眼科新进展,1995,15(1)：25-261
[20]肖继皋,吴树杨,王育良,汉防己甲素对实验性葡萄膜炎的治疗作用及机制,[J]1中华眼底病杂志,1994,10：1491
[19-20]宋艳,詹宇坚,古继红,葡萄膜炎与相关细胞因子的研究进展,中国中医眼科杂志2004年8月第14卷第3期
[21]周婉瑜,李越虹,麻柔,许勇钢,中药明目汤对白塞氏病葡萄膜炎患者T淋巴细胞亚群的影响,中国中西医结合杂志2002年9月第22卷第9期