牛磺鹅去氧胆酸对小鼠免疫细胞凋亡的影响
摘要
本研究旨在阐明牛磺鹅去氧胆酸(TCDCA)对小鼠免疫细胞凋亡的影响及其影响机理。采用二苯胺法检测了给药后小鼠不同免疫细胞的凋亡百分率,结果显示:低剂量TCDCA能够显著抑制正常小鼠腹腔巨噬细胞、脾脏淋巴细胞和血液淋巴细胞的凋亡,但对胸腺细胞凋亡无显著影响;高剂量TCDCA能够显著抑制正常小鼠外周血淋巴细胞的凋亡,对脾脏淋巴细胞凋亡无显著影响,但能够显著促进正常小鼠腹腔巨噬细胞和胸腺细胞的凋亡。表明TCDCA对不同的免疫细胞的凋亡具有不同的影响,显示出其免疫调节作用。
通过考察TCDCA对外周血淋巴细胞凋亡过程中Caspase依赖的内源性细胞凋亡途径的影响,探讨了其影响小鼠免疫细胞凋亡的机理。采用流式细胞仪检测了TCDCA对外周血液淋巴细胞凋亡早期磷脂酰丝氨酸外翻百分率的影响,证明低剂量和高剂量TCDCA均能够降低磷脂酰丝氨酸外翻百分率,用药后第4天,TCDCA对磷脂酰丝氨酸外翻百分率的抑制作用最显著;采用流式细胞仪检测了TCDCA对外周血淋巴细胞线粒体膜电位发生变化的百分率,证明低剂量TCDCA能够极显著的降低淋巴细胞线粒体膜势能变化百分率;采用分光光度法检测了TCDCA对外周血淋巴细胞凋亡过程中Caspase—3、Caspase—9蛋白酶的活化程度的影响,证明高、低剂量TCDCA均能极显著的抑制Caspase-9及Caspase-3蛋白酶活性。实验结果表明TCDCA对小鼠外周血淋巴细胞Caspase依赖的内源性细胞凋亡途径的不同时期、不同阶段均有显著的凋亡抑制作用。
To elucidate the influences of Taurochenodexycholic Acid (TCDCA) on apoptosis of immunocytes in mice and explain its principle are the aim of the experiment. The diphenylamine experiment was used for examining the percentage of apoptosis on different immunocytes after administer TCDCA. The results of this experiment are that TCDCA at low dose can inhibit the apoptosis of macrophage in abdominal cavity, lymphocyte both in blood and spleen, but have no effect on thymocyte; The high dose can inhibit the apoptosis of lymphocyte in blood, accelerate the apoptosis of thymocyte and macrophage in abdominal cavity, but has no effect on lymphocyte in spleen. The result show that TCDCA has different influences on apoptosis of different lymphocytes.
In order to clarify the theory of TCDCA working on apoptosis of immunocytes in mice, the way that TCDCA affect apoptosis of lymphocyte in blood by the intrinsin pathway, which Lean on Caspase, was researched. Flow Cytometry was used for examining the percentage of apoptosis on lymphcell in blood which Serine had evaginated after administer TCDCA, the result show that both the TCDCA at high dose and low dose can decrease the percentage of lymphcell in blood which serine had evaginated, and the most remarkable prohibitive influence appeared on four days after administer TCDCA. Flow Cytometry was also used for examining the percentage of the lymphocyte which plastochondria membrane electric potential changed after administer TCDCA, the result show that TCDCA at low dose can decrease the percentage of the lymphocyte plastochondria membrane electric potential changing; the method of spectrophotometer was used for examining the active of Caspase-9 and Caspase-3 after administer TCDCA , the result show that both the TCDCA at high dose and low dose can bate the active of Caspase-9 and Caspase-3 . In a word, TCDCA has remarkable inhibitory influence on apoptosis of lymphocyte in blood at different period.
通过考察TCDCA对外周血淋巴细胞凋亡过程中Caspase依赖的内源性细胞凋亡途径的影响,探讨了其影响小鼠免疫细胞凋亡的机理。采用流式细胞仪检测了TCDCA对外周血液淋巴细胞凋亡早期磷脂酰丝氨酸外翻百分率的影响,证明低剂量和高剂量TCDCA均能够降低磷脂酰丝氨酸外翻百分率,用药后第4天,TCDCA对磷脂酰丝氨酸外翻百分率的抑制作用最显著;采用流式细胞仪检测了TCDCA对外周血淋巴细胞线粒体膜电位发生变化的百分率,证明低剂量TCDCA能够极显著的降低淋巴细胞线粒体膜势能变化百分率;采用分光光度法检测了TCDCA对外周血淋巴细胞凋亡过程中Caspase—3、Caspase—9蛋白酶的活化程度的影响,证明高、低剂量TCDCA均能极显著的抑制Caspase-9及Caspase-3蛋白酶活性。实验结果表明TCDCA对小鼠外周血淋巴细胞Caspase依赖的内源性细胞凋亡途径的不同时期、不同阶段均有显著的凋亡抑制作用。
To elucidate the influences of Taurochenodexycholic Acid (TCDCA) on apoptosis of immunocytes in mice and explain its principle are the aim of the experiment. The diphenylamine experiment was used for examining the percentage of apoptosis on different immunocytes after administer TCDCA. The results of this experiment are that TCDCA at low dose can inhibit the apoptosis of macrophage in abdominal cavity, lymphocyte both in blood and spleen, but have no effect on thymocyte; The high dose can inhibit the apoptosis of lymphocyte in blood, accelerate the apoptosis of thymocyte and macrophage in abdominal cavity, but has no effect on lymphocyte in spleen. The result show that TCDCA has different influences on apoptosis of different lymphocytes.
In order to clarify the theory of TCDCA working on apoptosis of immunocytes in mice, the way that TCDCA affect apoptosis of lymphocyte in blood by the intrinsin pathway, which Lean on Caspase, was researched. Flow Cytometry was used for examining the percentage of apoptosis on lymphcell in blood which Serine had evaginated after administer TCDCA, the result show that both the TCDCA at high dose and low dose can decrease the percentage of lymphcell in blood which serine had evaginated, and the most remarkable prohibitive influence appeared on four days after administer TCDCA. Flow Cytometry was also used for examining the percentage of the lymphocyte which plastochondria membrane electric potential changed after administer TCDCA, the result show that TCDCA at low dose can decrease the percentage of the lymphocyte plastochondria membrane electric potential changing; the method of spectrophotometer was used for examining the active of Caspase-9 and Caspase-3 after administer TCDCA , the result show that both the TCDCA at high dose and low dose can bate the active of Caspase-9 and Caspase-3 . In a word, TCDCA has remarkable inhibitory influence on apoptosis of lymphocyte in blood at different period.
引文
1 俞长芳. 胆汁、牛黄与动物结石[M]. 北京:中国医药科技出版社,1991.3-32
2 刘养清,刘仁保.动物胆汁理化特性及药用.化学工业出版社.2002:5-8
3 李继衍.牛磺熊去氧胆酸结构及性质的研究.中国药科大学学报,1993,24(3):145-149
4 李培锋,哈斯苏荣等.鸡胆汁有效成分 CDCA 和 TCDCA 的提取及其抗炎作用研究.内蒙古农业大学学报,2000,21(4):68-71
5 郝丽莉,赵文静. 动物胆汁的药用研究[J]. 中国民族民间医药杂志,1999,40(4):279-280
6 张豁中,温玉麟.动物活性成分化学.天津科学技术出版社,1995:336-337
7 郝丽莉,赵文静等.具有开发价值的动物胆汁的药用研究.中国药学学报,2000,15(1):27-28
8 彭新磊.胆汁、胆酸和胆汁酸.生物学通报,1998,33(3):23-24
9 王凯平,石朝周.动物胆汁药用研究的概况与展望.中国中医药技.2000,7(5):350-352
10 张豁中,温玉麟.动物活性成分化学.天津科学技术出版社,1995:336-337
11 李培锋,关红,哈斯苏荣等.鸡胆汁的有效成分分析及其药理学研究.科研鉴定材 料,2001,12
12 李培锋,关红,哈斯苏荣等.鸡胆汁的药理作用研究[C].中国畜牧兽医学会第十届全国代表大会暨学术年会论文集,北京:中国农业大学出版社,1997:335-337
13 李培锋,哈斯苏荣等.鸡胆汁有效成分 CDCA 和 TCDCA 的提取及抗菌作用研究[J].内蒙古农业大学学报,2000,21(4):68-71.
14 黎 源 , 马 锦 星 , 石 朝 周 . 鸡 胆 汁 与 蛇 胆 汁 中 主 要 结 合 胆 汁 酸 含 量 对 比 [J]. 中 成 药,2003,25(5):420～421
15 斯琴. 牛磺酸鹅去氧胆酸的提取及其药理作用研究[D].硕士学位论文.内蒙古农业大学.2003.
16 何秀玲,李培锋,关红,金少琳.牛磺酸鹅去氧胆酸对小鼠免疫功能的影响[J].中药材,2005,28(12):1089-1092
17 黎源,马锦星,石朝周.鸡胆汁与蛇胆汁中主要结合胆汁酸含量对比[J]. 中成药,2003, 25(5): 20-421
18 Uchida A, Yamada T, Hayakawa T, et al. Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intetinal inflammation[J]. AM J PHYSOL-GASTR L,1997,35 (5): 1249-1257
19 Arndt H, Kullmann F, Scholmerich J, et al. Acute and chronic effects of different bile acids on indomethacin-induced intestinal inflammation[J]. INFLAMMATION,1997, 21(6): 553-567
20 梅和珊,石朝周,王凯平,向一,等. 牛磺胆酸钠和牛磺鹅去氧胆酸钠的药效学比较研究[J]. 中国生化药物杂志,1999, 20(4): 198-200
21 胡霞敏,石朝周. 牛磺结合及其游离胆汁酸在小鼠镇咳祛痰抗炎模型上的作用比较[J]. 中国临床药学杂志, 2001, 10(2): 85-88
22 何秀玲.TCDCA 抗炎免疫药理学及药代动力学研究[D]. 内蒙古农业大学博士学位论文.2006
23 李培锋,关红,赵红霞,等. 鸡胆汁有效成分 CDCA 和 TCDCA 的解热镇痛作用研究[J]. 内蒙古农业大学学报, 2001, 22(增刊): 1-5
24 斯琴,李培锋,关红. TCDCA 的镇咳、平喘和祛痰作用研究[J] .内蒙古农业大学学报(自然科学版),2001, 22(69)增刊: 26-29
25 荣康泰. 免疫药理学[M]. 杭洲:浙江科学技术出版社, 1987,14-17
26 关红,李培锋,哈斯苏荣, 贺文琦,等. 鸡胆汁有效成分的镇咳作用及对气管和肺组织中 PGE2含量的影响[J]. 内蒙古农业大学学报, 2001,22(增刊): 13-16
27 Kurktschiev D T, Temeldova-kurktschiev, Horn K, et al. Successful immunodulating in AIDS patients with ursodeoxycholic acid apilot study[J]. Clin Exp Immunol, 1999, 115: 144
28 Herold B C, Kirkpatrick R, Marcellino D, et al. Bile salts:naturea detergents for the prevent of sexually transmitted diseases[J]. Antimicrob Agents Chemother, 1999,
43 (4): 745
29 Funaoka M, Komatsu M, Toyoshima I, et al. Taurochenodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell[J]. Gastroen Hepatol, 1999, 14(7): 652-658
30 杨忠. 牛磺酸鹅去氧胆酸对小鼠体内氧自由基代谢的影响. 内蒙古农业大学硕士学位论文.2006
31 Xiao Z L, Biancani P, Behar J. Effects and mechanisms of action of taurochenodeoxycholic acid on guinea pig gallbladder muscle[J]. Gastroenterology, 2000, 118(4): A202-A203
32 Sagawa H, et al. [J]. Am J Physiol, 264(5): 835-839
33 Poupoon PE, Yves C, Poupon R, et al. [J]. Hepatology, 1993,17(4): 599-604
34 于善谦 王洪海 朱乃硕 叶荣. 免疫学导论[M]. 北京. 高等教育出版社.1999.7
35 Abele R, Tampe R. Modulation of the antigen transport machinery TAP by friends and enemies.FEBS Lett. 2006 Feb 13;580(4):1156-1163.
36 Karnes RJ, Whelan CM, Kwon ED. Immunotherapy for prostate cancer.Curr Pharm Des. 2006;12(7):807-817.
37 Raimondi G, Turner MS,Thomson AW, Morel PA. Naturally occurring regulatory T cells: recent insights in health and disease.Crit Rev Immunol. 2007;27(1):61-95.
38 陈慰峰.医学免疫学 [M] 北京.人民卫生出版社 .2005-1-1
39 Burchill MA, Yang J, Vogtenhuber C, Blazar BR, Farrar MA. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells.J Immunol. 2007 Jan 1;178(1):280-290.
40 Besedovsky H. Network of immune-neuroendocrine interactions. Clinical and Experimental Immunology.1977 , 27 , 161-167
41 余传霖 陆德源 陆德源. 现代医学免疫学[M].上海:上海医科大学出版社. 1998.6
42 秦 卫 松 ; 郑 春 霞 .T 细 胞 调 节 免 疫 应 答 的 机 制 [J]. 肾 脏 病 与 透 析 肾 移 植 杂志.2006,5:452-456
43 吴祖群. 调节性 T 细胞研究进展[J]. 现代免疫学 , 2004,(01)
44 Watt V, Ronchese F, Ritchie D. Resting B cells suppress tumor immunity via an MHC class-II dependent mechanism.J Immunother. 2007 Apr;30(3):323-332.
45 [美]L.松佩拉克著 李琦涵 施海晶等译. 免疫学概览 (原著第 2 版)[M]. 化学工业出版社 现代生物技术与医药科技出版中心, 2005.
46 陆江阳,梁延杰.多器官衰竭早期免疫器官细胞凋亡的检测及意义[J].解放军医学杂志,1996,21(6):414-415
47 姜泊.细胞凋亡的基础与临床[M].北京:人民军医出版社,1999
48 翟中和,王喜中,丁明孝.细胞生物学[M].北京:高等教育出版社,2000:454-459.
49 何维敬, 张庆殷. 如何区分凋亡细胞与坏死细胞[J]. 江西医学检验 , 1999,(04)
50 彭黎明. 细胞凋亡检测的研究进展[J]. 中华医学检验杂志 , 1996,(06)
51 袁海波; 沈忠明.细胞凋亡的分子机理[J]. 上海大学学报(自然科学版),2001,(1):76-80
52 吴 红 . 细 胞 凋 亡 的 信 号 传 导 及 其 基 因 表 达 调 控 作 用 研 究 [J]. 实 用 临 床 医学.2006(4):143-145
53 Pastorino J G,Hoek T B.Mitochondrial binding of hexokinase indibits Bax-incloud cytochrome release andapoptosis[J].,J Biol Chem, 2002, 277: 7610-7618
54 刘静,唐兆新.线粒体在细胞凋亡中的作用[J].动物医学进展.2006,27(6):42-45
55 郭淑贞,曾定.Caspase 家族与细胞凋亡[J] .细胞生物学杂志 1999(21) 4 :163-169
56 Awasaki T, Tatsumi R, Takahashi K, Arai K, Nakanishi Y, Ueda R, Ito K. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis[J] Neuron.. 2006;50(6):819-821.
57 Haddad JJ.The Role of Bax/Bcl-2 and Pro-Caspase Peptides in Hypoxia/Reperfusion-Dependent Regulation of MAPK(ERK): Discordant Proteomic Effect of MAPK(p38)[J].Protein Pept Lett. 2007;14(4):361-371.
58 Abdullah JM, Ahmad F, Ahmad KA, Ghazali MM, Jaafar H, Ideris A, Ali AM, Omar AR, Yusoff K, Lila MA, Othman F. Molecular genetic analysis of BAX and cyclin D1 genesin patients with malignant glioma[J].Neurol Res. 2007 29(3):239-242.
59 Furuya Y, Isaacs JT.Differential gene regulation during programmed death (apoptosis) versus proliferation of prostatic glandular cells induced by androgen manipulation[J].Endocrinology. 1993 Dec;133(6):2660-2666.
60 Albitar L, Carter MB, Davies S, Leslie KK.Consequences of the loss of p53, RB1, and PTEN: Relationship to gefitinib resistance in endometrial cancer.[J]. Gynecol Oncol. 2007, 7:355-359
61 Yang P, Cartwright C, Chan D, Vijjeswarapu M, Ding J, Newman RA.Zyflamend((R))-Mediated Inhibition of Human Prostate Cancer PC3 Cell Proliferation: Effects on 12-LOX and Rb Protein Phosphorylation.[J].Cancer Biol Ther. 2007 Feb;6(2):228-36.
62 石有斐..牛磺鹅去氧胆酸对小鼠免疫功能的调节作用[J](中国药理学通报,已录用)
63 王庸晋 , 魏武 , 王治平 , 公惠平. 氧化型极低密度脂蛋白诱导小鼠腹腔巨噬细胞凋亡[J]. 动脉硬化杂志 2004 ,12 ( 1 ):20
64 刘艳红.二苯胺法定量检测细胞凋亡[J].武汉大学学报,2002,23(1):63-64
65 刘玉涛,周东,白小薇等.枸杞多糖对小鼠胸腺细胞凋亡的调节[J].北京医科大学学报,1996,28(2)B11
66 孙江波,马 骥,张玲玲. 紫癜颗粒对模型小鼠脾脏淋巴细胞凋亡的影响[J]. 辽宁中医杂志.2006,33(6):752-753
67 Sudeepta Aggarwal, Abha Gupta. Programmed cell Death in cord Blood lymphocytes. Journal of clinical Immunology, Volume 17 Number 1:63-73
68 李莉,孔宪涛.细胞凋亡检测方法评价[J]. 上海医学检验杂志 2000,15(1):73-75
69 Palmer AM, Gieengrass PM,Cnvalla D. The rule of mitochondria in apoptosis[J]. Drug News Perspect, 2000,13(6):378-384.
70 Hakem R, Hakem A, Dnncan GS, et al.Differential requirement for caspasc -9 in apoptotic pathways in vivo[J] .Cell, 1998, 94(3):339-352
71 Maier ,JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a dlirect inhibitor of caspase 3 and 7[J].J Neuro Sci,2002, 22( 6):2035- 2043.
72 石有斐. 牛磺鹅去氧胆酸对小鼠免疫功能的调节作用及其机理研究[D]. 内蒙古农业大学博士学位论文.2007
2 刘养清,刘仁保.动物胆汁理化特性及药用.化学工业出版社.2002:5-8
3 李继衍.牛磺熊去氧胆酸结构及性质的研究.中国药科大学学报,1993,24(3):145-149
4 李培锋,哈斯苏荣等.鸡胆汁有效成分 CDCA 和 TCDCA 的提取及其抗炎作用研究.内蒙古农业大学学报,2000,21(4):68-71
5 郝丽莉,赵文静. 动物胆汁的药用研究[J]. 中国民族民间医药杂志,1999,40(4):279-280
6 张豁中,温玉麟.动物活性成分化学.天津科学技术出版社,1995:336-337
7 郝丽莉,赵文静等.具有开发价值的动物胆汁的药用研究.中国药学学报,2000,15(1):27-28
8 彭新磊.胆汁、胆酸和胆汁酸.生物学通报,1998,33(3):23-24
9 王凯平,石朝周.动物胆汁药用研究的概况与展望.中国中医药技.2000,7(5):350-352
10 张豁中,温玉麟.动物活性成分化学.天津科学技术出版社,1995:336-337
11 李培锋,关红,哈斯苏荣等.鸡胆汁的有效成分分析及其药理学研究.科研鉴定材 料,2001,12
12 李培锋,关红,哈斯苏荣等.鸡胆汁的药理作用研究[C].中国畜牧兽医学会第十届全国代表大会暨学术年会论文集,北京:中国农业大学出版社,1997:335-337
13 李培锋,哈斯苏荣等.鸡胆汁有效成分 CDCA 和 TCDCA 的提取及抗菌作用研究[J].内蒙古农业大学学报,2000,21(4):68-71.
14 黎 源 , 马 锦 星 , 石 朝 周 . 鸡 胆 汁 与 蛇 胆 汁 中 主 要 结 合 胆 汁 酸 含 量 对 比 [J]. 中 成 药,2003,25(5):420～421
15 斯琴. 牛磺酸鹅去氧胆酸的提取及其药理作用研究[D].硕士学位论文.内蒙古农业大学.2003.
16 何秀玲,李培锋,关红,金少琳.牛磺酸鹅去氧胆酸对小鼠免疫功能的影响[J].中药材,2005,28(12):1089-1092
17 黎源,马锦星,石朝周.鸡胆汁与蛇胆汁中主要结合胆汁酸含量对比[J]. 中成药,2003, 25(5): 20-421
18 Uchida A, Yamada T, Hayakawa T, et al. Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intetinal inflammation[J]. AM J PHYSOL-GASTR L,1997,35 (5): 1249-1257
19 Arndt H, Kullmann F, Scholmerich J, et al. Acute and chronic effects of different bile acids on indomethacin-induced intestinal inflammation[J]. INFLAMMATION,1997, 21(6): 553-567
20 梅和珊,石朝周,王凯平,向一,等. 牛磺胆酸钠和牛磺鹅去氧胆酸钠的药效学比较研究[J]. 中国生化药物杂志,1999, 20(4): 198-200
21 胡霞敏,石朝周. 牛磺结合及其游离胆汁酸在小鼠镇咳祛痰抗炎模型上的作用比较[J]. 中国临床药学杂志, 2001, 10(2): 85-88
22 何秀玲.TCDCA 抗炎免疫药理学及药代动力学研究[D]. 内蒙古农业大学博士学位论文.2006
23 李培锋,关红,赵红霞,等. 鸡胆汁有效成分 CDCA 和 TCDCA 的解热镇痛作用研究[J]. 内蒙古农业大学学报, 2001, 22(增刊): 1-5
24 斯琴,李培锋,关红. TCDCA 的镇咳、平喘和祛痰作用研究[J] .内蒙古农业大学学报(自然科学版),2001, 22(69)增刊: 26-29
25 荣康泰. 免疫药理学[M]. 杭洲:浙江科学技术出版社, 1987,14-17
26 关红,李培锋,哈斯苏荣, 贺文琦,等. 鸡胆汁有效成分的镇咳作用及对气管和肺组织中 PGE2含量的影响[J]. 内蒙古农业大学学报, 2001,22(增刊): 13-16
27 Kurktschiev D T, Temeldova-kurktschiev, Horn K, et al. Successful immunodulating in AIDS patients with ursodeoxycholic acid apilot study[J]. Clin Exp Immunol, 1999, 115: 144
28 Herold B C, Kirkpatrick R, Marcellino D, et al. Bile salts:naturea detergents for the prevent of sexually transmitted diseases[J]. Antimicrob Agents Chemother, 1999,
43 (4): 745
29 Funaoka M, Komatsu M, Toyoshima I, et al. Taurochenodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell[J]. Gastroen Hepatol, 1999, 14(7): 652-658
30 杨忠. 牛磺酸鹅去氧胆酸对小鼠体内氧自由基代谢的影响. 内蒙古农业大学硕士学位论文.2006
31 Xiao Z L, Biancani P, Behar J. Effects and mechanisms of action of taurochenodeoxycholic acid on guinea pig gallbladder muscle[J]. Gastroenterology, 2000, 118(4): A202-A203
32 Sagawa H, et al. [J]. Am J Physiol, 264(5): 835-839
33 Poupoon PE, Yves C, Poupon R, et al. [J]. Hepatology, 1993,17(4): 599-604
34 于善谦 王洪海 朱乃硕 叶荣. 免疫学导论[M]. 北京. 高等教育出版社.1999.7
35 Abele R, Tampe R. Modulation of the antigen transport machinery TAP by friends and enemies.FEBS Lett. 2006 Feb 13;580(4):1156-1163.
36 Karnes RJ, Whelan CM, Kwon ED. Immunotherapy for prostate cancer.Curr Pharm Des. 2006;12(7):807-817.
37 Raimondi G, Turner MS,Thomson AW, Morel PA. Naturally occurring regulatory T cells: recent insights in health and disease.Crit Rev Immunol. 2007;27(1):61-95.
38 陈慰峰.医学免疫学 [M] 北京.人民卫生出版社 .2005-1-1
39 Burchill MA, Yang J, Vogtenhuber C, Blazar BR, Farrar MA. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells.J Immunol. 2007 Jan 1;178(1):280-290.
40 Besedovsky H. Network of immune-neuroendocrine interactions. Clinical and Experimental Immunology.1977 , 27 , 161-167
41 余传霖 陆德源 陆德源. 现代医学免疫学[M].上海:上海医科大学出版社. 1998.6
42 秦 卫 松 ; 郑 春 霞 .T 细 胞 调 节 免 疫 应 答 的 机 制 [J]. 肾 脏 病 与 透 析 肾 移 植 杂志.2006,5:452-456
43 吴祖群. 调节性 T 细胞研究进展[J]. 现代免疫学 , 2004,(01)
44 Watt V, Ronchese F, Ritchie D. Resting B cells suppress tumor immunity via an MHC class-II dependent mechanism.J Immunother. 2007 Apr;30(3):323-332.
45 [美]L.松佩拉克著 李琦涵 施海晶等译. 免疫学概览 (原著第 2 版)[M]. 化学工业出版社 现代生物技术与医药科技出版中心, 2005.
46 陆江阳,梁延杰.多器官衰竭早期免疫器官细胞凋亡的检测及意义[J].解放军医学杂志,1996,21(6):414-415
47 姜泊.细胞凋亡的基础与临床[M].北京:人民军医出版社,1999
48 翟中和,王喜中,丁明孝.细胞生物学[M].北京:高等教育出版社,2000:454-459.
49 何维敬, 张庆殷. 如何区分凋亡细胞与坏死细胞[J]. 江西医学检验 , 1999,(04)
50 彭黎明. 细胞凋亡检测的研究进展[J]. 中华医学检验杂志 , 1996,(06)
51 袁海波; 沈忠明.细胞凋亡的分子机理[J]. 上海大学学报(自然科学版),2001,(1):76-80
52 吴 红 . 细 胞 凋 亡 的 信 号 传 导 及 其 基 因 表 达 调 控 作 用 研 究 [J]. 实 用 临 床 医学.2006(4):143-145
53 Pastorino J G,Hoek T B.Mitochondrial binding of hexokinase indibits Bax-incloud cytochrome release andapoptosis[J].,J Biol Chem, 2002, 277: 7610-7618
54 刘静,唐兆新.线粒体在细胞凋亡中的作用[J].动物医学进展.2006,27(6):42-45
55 郭淑贞,曾定.Caspase 家族与细胞凋亡[J] .细胞生物学杂志 1999(21) 4 :163-169
56 Awasaki T, Tatsumi R, Takahashi K, Arai K, Nakanishi Y, Ueda R, Ito K. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis[J] Neuron.. 2006;50(6):819-821.
57 Haddad JJ.The Role of Bax/Bcl-2 and Pro-Caspase Peptides in Hypoxia/Reperfusion-Dependent Regulation of MAPK(ERK): Discordant Proteomic Effect of MAPK(p38)[J].Protein Pept Lett. 2007;14(4):361-371.
58 Abdullah JM, Ahmad F, Ahmad KA, Ghazali MM, Jaafar H, Ideris A, Ali AM, Omar AR, Yusoff K, Lila MA, Othman F. Molecular genetic analysis of BAX and cyclin D1 genesin patients with malignant glioma[J].Neurol Res. 2007 29(3):239-242.
59 Furuya Y, Isaacs JT.Differential gene regulation during programmed death (apoptosis) versus proliferation of prostatic glandular cells induced by androgen manipulation[J].Endocrinology. 1993 Dec;133(6):2660-2666.
60 Albitar L, Carter MB, Davies S, Leslie KK.Consequences of the loss of p53, RB1, and PTEN: Relationship to gefitinib resistance in endometrial cancer.[J]. Gynecol Oncol. 2007, 7:355-359
61 Yang P, Cartwright C, Chan D, Vijjeswarapu M, Ding J, Newman RA.Zyflamend((R))-Mediated Inhibition of Human Prostate Cancer PC3 Cell Proliferation: Effects on 12-LOX and Rb Protein Phosphorylation.[J].Cancer Biol Ther. 2007 Feb;6(2):228-36.
62 石有斐..牛磺鹅去氧胆酸对小鼠免疫功能的调节作用[J](中国药理学通报,已录用)
63 王庸晋 , 魏武 , 王治平 , 公惠平. 氧化型极低密度脂蛋白诱导小鼠腹腔巨噬细胞凋亡[J]. 动脉硬化杂志 2004 ,12 ( 1 ):20
64 刘艳红.二苯胺法定量检测细胞凋亡[J].武汉大学学报,2002,23(1):63-64
65 刘玉涛,周东,白小薇等.枸杞多糖对小鼠胸腺细胞凋亡的调节[J].北京医科大学学报,1996,28(2)B11
66 孙江波,马 骥,张玲玲. 紫癜颗粒对模型小鼠脾脏淋巴细胞凋亡的影响[J]. 辽宁中医杂志.2006,33(6):752-753
67 Sudeepta Aggarwal, Abha Gupta. Programmed cell Death in cord Blood lymphocytes. Journal of clinical Immunology, Volume 17 Number 1:63-73
68 李莉,孔宪涛.细胞凋亡检测方法评价[J]. 上海医学检验杂志 2000,15(1):73-75
69 Palmer AM, Gieengrass PM,Cnvalla D. The rule of mitochondria in apoptosis[J]. Drug News Perspect, 2000,13(6):378-384.
70 Hakem R, Hakem A, Dnncan GS, et al.Differential requirement for caspasc -9 in apoptotic pathways in vivo[J] .Cell, 1998, 94(3):339-352
71 Maier ,JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a dlirect inhibitor of caspase 3 and 7[J].J Neuro Sci,2002, 22( 6):2035- 2043.
72 石有斐. 牛磺鹅去氧胆酸对小鼠免疫功能的调节作用及其机理研究[D]. 内蒙古农业大学博士学位论文.2007