褪黑素对脂多糖刺激小鼠抗氧化与免疫功能的影响
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摘要
本文研究了褪黑素对LPS刺激小鼠氧化应激和免疫功能的的调节作用,并分析了他们之间的相关性,进一步通过对氧化还原及免疫相关基因的表达的影响探讨其可能的保护机制。
选用清洁级三周龄雄性昆明小鼠70只,分成四组:正常组、生理盐水组、低褪黑素组、高褪黑素组。预饲一周后,生理盐水组每天灌胃生理盐水0.2 mL;低褪黑素组每天灌胃1 mg/kg.BW的褪黑素;高褪黑素组每天灌胃2 mg/kg.BW的褪黑素。灌胃三周后,除正常组外,每组均腹腔注射5 mg/kg.BW的LPS 0.2 mL,正常组腹腔注射同剂量的无菌生理盐水,注射后4、16 h,测定机体活性氧(ROS)水平、抗氧化能力;采用ELISA检测血浆中IL-1、TNF-α、IL-10的含量;实时定量PCR检测肝脏金属硫蛋白1(Mt1)、核转录因子-B(NF-κB)、热激蛋白70(HSP70)和转录活化蛋白-1(AP-1)基因表达。
实验结果:(1)褪黑素可以显著降低LPS刺激小鼠机体的ROS水平,增强抗氧化酶的活性,提高机体的抗氧化能力。(2)褪黑素可以显著降低LPS刺激小鼠十二指肠MPO活性,抑制血浆炎性细胞因子IL-6、TNF-α分泌,促进抗炎性细胞因子IL-10的分泌,从而减轻机体的炎性损伤。(3)褪黑素可以使LPS刺激小鼠肝脏Mt1 mRNA表达上调、NF-κB mRNA、HSP70 mRNA、AP-1 mRNA表达下调,从而保护机体,改善LPS导致的氧化和炎性损伤。
结论:腹腔注射脂多糖,引起机体的急性炎症反应、降低抗氧化能力,导致免疫功能状态失调。而灌胃褪黑素可有效清除LPS诱导的机体过量产生的ROS,提高机体抗氧化能力,并抑制炎性细胞因子的分泌,改善免疫功能。其可能机制为褪黑素通过调节相关基因的表达,改善抗氧化与免疫功能。
This investigation was conducted to evaluate the effect of melatonin on the oxidative stress, immune function of mice under the stimulation of lipopolysaccharide, in addition, the possible mechanism was analyzed by the relative gene expression.
70 male mice were randomly divided into 4 groups. The control group was fed with basal diet and the other three groups were given with saline respectively, 1mg/kg.BW of Melatonin, 2mg/kg.BW of melatonin. After 3 weeks, the control group was injected with saline intraperitoneally, and the other groups were injected with 0.2ml 5mg/kg.BW of LPS intraperitoneally. After 4 and 16 hours, the ROS levels of blood and organs, the anti-oxidative capacity in plasma and organs were determined. The levels of IL-1, TNF-αand IL-10 in plasma were assayed by ELISA. In order to explore the molecular mechanisms underlying the modulating effect of melatonin on oxidative stress and immune dysfunction induced by LPS, the expression of Mt1, NF-κB, HSP70 and AP-1 in liver of mice by quantitative real-time reverse transcription–polymerase chain reaction was determined by melatonin.
The results were as follows: (1) The levels of ROS produced in blood and organs were decreased, and the anti-oxidative capacity of mice under the stimulation of LPS were decreased by melatonin. (2) The contents of inflammatory cytokine interleukin-1 (IL-1) and tumor necrosis factor-α(TNF-α) decreased relatively, and anti-inflammatory cytokine interleukin-10 (IL-10) increased with the supplement of melatonin in mice. (3)The expression of Mt1 in liver significantly lowered and the expressions of NFκB, HSP70 and AP-1 significantly increased in mice under the stimulation of Lipopolysaccharide.
Conclusion: Lipopolysaccharide resulted in oxidative stress and dysfunction in immune system. The optimum dose of Melatonin could be able to eliminate the excessive ROS, increase the anti-oxidative capacity, regulate the immune dysfunction of mice under the stimulation of Lipopolysaccharide.
选用清洁级三周龄雄性昆明小鼠70只,分成四组:正常组、生理盐水组、低褪黑素组、高褪黑素组。预饲一周后,生理盐水组每天灌胃生理盐水0.2 mL;低褪黑素组每天灌胃1 mg/kg.BW的褪黑素;高褪黑素组每天灌胃2 mg/kg.BW的褪黑素。灌胃三周后,除正常组外,每组均腹腔注射5 mg/kg.BW的LPS 0.2 mL,正常组腹腔注射同剂量的无菌生理盐水,注射后4、16 h,测定机体活性氧(ROS)水平、抗氧化能力;采用ELISA检测血浆中IL-1、TNF-α、IL-10的含量;实时定量PCR检测肝脏金属硫蛋白1(Mt1)、核转录因子-B(NF-κB)、热激蛋白70(HSP70)和转录活化蛋白-1(AP-1)基因表达。
实验结果:(1)褪黑素可以显著降低LPS刺激小鼠机体的ROS水平,增强抗氧化酶的活性,提高机体的抗氧化能力。(2)褪黑素可以显著降低LPS刺激小鼠十二指肠MPO活性,抑制血浆炎性细胞因子IL-6、TNF-α分泌,促进抗炎性细胞因子IL-10的分泌,从而减轻机体的炎性损伤。(3)褪黑素可以使LPS刺激小鼠肝脏Mt1 mRNA表达上调、NF-κB mRNA、HSP70 mRNA、AP-1 mRNA表达下调,从而保护机体,改善LPS导致的氧化和炎性损伤。
结论:腹腔注射脂多糖,引起机体的急性炎症反应、降低抗氧化能力,导致免疫功能状态失调。而灌胃褪黑素可有效清除LPS诱导的机体过量产生的ROS,提高机体抗氧化能力,并抑制炎性细胞因子的分泌,改善免疫功能。其可能机制为褪黑素通过调节相关基因的表达,改善抗氧化与免疫功能。
This investigation was conducted to evaluate the effect of melatonin on the oxidative stress, immune function of mice under the stimulation of lipopolysaccharide, in addition, the possible mechanism was analyzed by the relative gene expression.
70 male mice were randomly divided into 4 groups. The control group was fed with basal diet and the other three groups were given with saline respectively, 1mg/kg.BW of Melatonin, 2mg/kg.BW of melatonin. After 3 weeks, the control group was injected with saline intraperitoneally, and the other groups were injected with 0.2ml 5mg/kg.BW of LPS intraperitoneally. After 4 and 16 hours, the ROS levels of blood and organs, the anti-oxidative capacity in plasma and organs were determined. The levels of IL-1, TNF-αand IL-10 in plasma were assayed by ELISA. In order to explore the molecular mechanisms underlying the modulating effect of melatonin on oxidative stress and immune dysfunction induced by LPS, the expression of Mt1, NF-κB, HSP70 and AP-1 in liver of mice by quantitative real-time reverse transcription–polymerase chain reaction was determined by melatonin.
The results were as follows: (1) The levels of ROS produced in blood and organs were decreased, and the anti-oxidative capacity of mice under the stimulation of LPS were decreased by melatonin. (2) The contents of inflammatory cytokine interleukin-1 (IL-1) and tumor necrosis factor-α(TNF-α) decreased relatively, and anti-inflammatory cytokine interleukin-10 (IL-10) increased with the supplement of melatonin in mice. (3)The expression of Mt1 in liver significantly lowered and the expressions of NFκB, HSP70 and AP-1 significantly increased in mice under the stimulation of Lipopolysaccharide.
Conclusion: Lipopolysaccharide resulted in oxidative stress and dysfunction in immune system. The optimum dose of Melatonin could be able to eliminate the excessive ROS, increase the anti-oxidative capacity, regulate the immune dysfunction of mice under the stimulation of Lipopolysaccharide.
引文
1. Simoneanx V,Ribelayga C.Generation of the melatonin endcrine message inmagro-mals:a review of the melatonin regulation of melatonin synthesis nonorepinephrine,poptides,and other pineal transimitters[J].Pharmacol Rev,2003,55(2):325-395
2.魏涛,唐芬芳,金宗濂.褪黑素的生理功能[J].食品工业科技,2001,23(9):98-102
3.刘作易,梁宗琦.褪黑素的研究开发现状[J].生命化学,2001,21(1):69-70
4. Reiter R J.Remembrance:Growing up with the pineal gland[J].Endocrinol,1992,131 (5):2039-2041
5. Tan D X,Chen L D,Poeggeler B,et al.Melatonin:a potent,endogenous hydroxyl radical scavenger[J].Endocrinol J,1993,1(1):57-60
6. Russel J B,Dun X T,Carmen O,et al.Action of melatonin in the reduction of oxidation stress[J].Biomed Sci,2000,7(1):444-458
7. Reiter R,Tang L,Garcia J J ,et al.Pharma-cological actions of melatonin in oxygen radical pathophysiology[J].L ife Sci,1997,60(1):2255-2271
8. Hardeland R. Antioxidative protection by melatonin:multip licity of mechanisms from radical detoxification to radical avoidance[J].Endocrine,2005,27(2):119-130
9. Tomas-Zapico C,Coto-Montes A.A proposed mechanism to explain the stimulatory eff-ect of melatonin on antioxidative enzymes[J].J Pineal Res,2005,39(3):99-104
10. Hardeland R,Pandi-Perumal S R,Cardinali D P.Melatonin[J].Int J Biochem Cell Biol,20-06,38(3):313-316
11. Suzen S,Bozkaya P,Coban T,Nebiogu D.Investigation of the in vitro antioxidant behaviour of some 2-phenylindole derivatives: discussion on possible antioxidant mechanisms and compa- rison with melatonin[J].J Enzyme Inhib Med Chen ,2006,21(4):405-411
12. IanasO,Olnescu R,Badescu L.Melatonin involvement in oxidative stress[J].Rom J Endocrino- l,1991,29:147-153
13. Rriter R J,Tan D X,Poeggeler B, et al.Melatonin as a free radical scavenge: Imp lications for aging and age-related diseases[J].Ann NY Acad Sci,1994,719:1-12
14.陈泳宏,刘平.褪黑素在临床中的应用[J].中国临床康复,2003,7(4):654-655
15. Maharaj D S,Anoopkumar-Dukie S,Glass B D,et al.The identification of the UV degra-dants of melatonin and their ability to scavenge radicals[J].J Pineal Res,2002,32:257-261
16. Tomas-Zapico C,Coto-Montes A.A proposed mechanism to explain the stimulatory effe-ct of melatonin on antioxidative enzymes[J].J Pineal Res,2005,39(2):99-104
17. Tocharus,Jiraporn,Chongthammakun,et al.Melatonin inhibits amphetamine2 induced nitri-c oxide synthase mRNA overexp ression in microglial cell lines[J].NeuroscienceLetters,2008,439(2):134-137
18. OzdemirD,UysalN,Tugyan K,et al.The efect of melatonin on endo toxemia induced int-estinal apoptosis and oxidative stress in infant rats[J].Intensive CareMed,2007,33:63-84
19. Wang H,Wei W,Zhang S Y,et al.Melatonin-selenium nanoparticles inhibit oxidativestres-s and protect against hepatic injury induced by Bacillus Calmette2 Guerin/lipopolysaccharide in mice[J].J Pineal Reso,2005,39(2):156-163
20. Othman A I,al Sharawy S,el-Missiry M A.Role of melatonin in ameliorating lead indu-ced haematotoxicity[J].Pharmacol Res,2004,50(3):301-307
21. Oner H,Kus I,Oner J,Ogeturk M,Ozan E,Ayar A.Possible efects of melatonin on thym-us gland after pinealectomy in rats[J].Neum Endocrinol Lett,2004,25(1-2):115-118
22. Haldar C,SirIgh R.Pineal modulatin of thymus and immune function in aseasonallybreeding tropical rodent,Funambulus pennantic[J].J Exp Zool,2001,289(2):90-98
23. Brennan C P,Hedricks G L,EL-Sheikh T M,Mashaly M M.Melatonin and the enchan- cement of immune responses in immature male chickens[J].Pouh Sci,2002,81(3):371-375
24. Trubiani O,Recchioni R,Moroni F,Pizzicannella J,Caputi S,Di Primio R. Melatonin pro-vokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pat-hway activation[J].J Pineal Res,2005,39(4):425–431
25. Maestroni G J.Eimmunotherapeutic potential of melatonin[J].Export Opin-lnvestig Drug-s,2001,10(3):467-476
26. Negrette B,Bonilla E,Valero N,Pons H,Garcia Tamayo J,Chacin Bonilla L,eta1.Melatoni-n treatment enhances the efficiency of mice immunization with Vnezuelan equine enc-ephalomyelitis virus TC-83[J].Neurochem Res,2001,26(7):767-770
27. Akbuut K G,Gonul B,Akbuut H.The efects of melatonin on humoral immune responses of young and aged rats[J].1mmunol Invest,2001,30(1):17-20
28. Baltaci AK,Mogulkoc R,Bediz CS,Pekel A.Efects of zinc deftciency and pinealectomy on cellular immunity in rats infected with Toxoplasma gondii[J].Biol Trace Elem Res,2005,104(1):47-56
29. Litvinenko G I,Shurlygina A V,Verbitskaya L V,Panteleeva N G,Melnikova E V,Trufakin V A. Circadian dynamics of cell composition of the thymus an d lymph nodes in mice normally,under conditions of permanent illumination,and after melatonin injection[J].Bull Exp Biol Med,2005,140(2):213-216
30. HuangY S,Jiang J W,Wu G C,Cao X D.Effect of melatonin and electro acupuncture (EA) on NK cell activity,interleukin-2 prduction and POMC derived peptides in traumatic rats[J].Acapunct Electrotller Res,2002,27(2):95-105
31. Srinivasan V,Maestroni G,Cardinali D,Esquifino A,Perumal SP,MiUer S.Mel-atonin,immune function and aglng[J]Lmmun Ageing,2005,2:17
32. Arias J,Melean E,Valero N,Pons H,Chacin-Bonilla L,Larreal Y,et a1. Efect of melatonin on lymphocyte proliferation an d production of interleukin-2(IL-2)and interleukin-l beta(IL-lbeta) in mice splenocytes[J].Invest Clin,2003,44(1):41-50
33. Carrillo-Vico A,Lardone P J,Naji L,Fernandez-Santos J M,Martin-Laeave I,Guerrero J M,et a1.Beneftcial pleiotropic actions of melatonin in an experi-mental model of septi-c shock in mice:regulation of pro-/antiinflammatory c-ytokine network,protection agains-t oxidative damage and anti-apoptotic efec-ts[J].J PineaRes,2005,39(4):400-408
34. Garcia-Maurino S.Mecatonin enhances IL-2,IL-6,and IFN-gamms production by humancirculating CD4 cells,a possible nuclear receptor-med iatied mechanism involving Thel-per type 1 lymphocytesand monocytes[J].J lmmunol,1997,159(2):574-581
35. Shaji A V,Kulkarni S K,Agrewala J N.Regulation of secretion of IL-4 and IgG1 isoty-pe by melation-stimulated ovalbumin-specipic T cells[J].Clin Exp lmmunol,1998,111(1):181-185
36. Dimitrov S,Lange T,Tieken S,Fehm H L,Born J. Sleep associated regulationof T helpe-r 1/T helper 2 cytokine balance in humans[J].Brain Behav lmmun,2004,18(5):341-348
37. Rodriguez-Iturbe B,Zhan C D,Quiroz Y,et al.Antioxidant-rish diet relieves hypertensionand reduces renal immune infiltration in spontaneously hypertensive rat [J].Hypertensio-n,2003,41(2):341-346
38. Stolk J,Seersholm N,Kalsheker N.Alphal-antitrypsin deficiency current perspective on research,diagnosis,and management[J].Chron Obstruct Pulmon Dis,2006, 1(2):151-160
39. May M J,Ghosh S.Signal transduction through NF-kappa B[J].Immunol Today,1998,19:80-88
40. Savill J.Apoptosis in resolution of inflammation[J].Journal of Leucocyte Biology,1997,61(4):375-380
41.慕宁,王海梁,傅宏,等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏[J].第二军医大学学报,2008,29(12):1429-1432
42. Lakshminarayanan V,Drab-Weiss E A,Roebuck K A.H2O2 and tumor necrosis factoralp-ha induce differential binding of the redox-responsive transcription factors AP-1and NF-kappaB to the interleukin-8 promoter in endothelialand epithelial cells[J].J Bio Chem,1998,273(49):32670-32678
43.李振,蔡小嫦.Th1/Th2细胞在炎症浸润中的不同表现[J].国外医学免疫学分册,2002,25(1):36-38
44. Zabel U,Henkel T,Silva M S,et al.Nuclear uptake control of NF-kappaB by MAD-3,and NF-kappaB protein present in the nucleus[J].EMBO J ,1993,12:201-211
45. Bloomfield G L,Holloway S,Ridings P C,et al.Pretreatment with inhaled nitric oxide inhibits neutrophil migration and oxidative activity resulting in attenuated sepsis-induce-d acute lung injury[J].Crit Care Med,1997,25:584-593
46.吴惠,杨向红,董玉兰,等.脂质过氧化对人血管内皮细胞NO合成的影响及维生素E的作用[J].中华病理学杂志,2002,31:260-261
47.胡文秀,杨成旺.大肠癌组织中HSP70和p53蛋白的表达及其意义[J].肿瘤防治研究,2007,5:363-365
48.傅庆国,孟凡东,郭克建,等.热休克蛋白70在诱导肿瘤免疫中的效应[J].中华微生物学和免疫学杂志,2003,23(1):31-33
49.黄晓兵,候梅.热休克蛋白与肿瘤细胞凋亡[J].四川肿瘤防治,2003,16(1):53-55
50. Arnott C H,Scott K A,Moore R J,et a1.Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha-and AP-1-dependent pathway[J].Oncogene,2002,21(31):4728-47 38
51. Chinenov Y,Kerppola T K.Close encounters of many kinds:Fos-Jun interactions that mediate transcrip tion regulatory specificity[J].Oncogene,2001,20(19):2438-2452
52.董淑红,苏力,魏克伦等.新生大鼠内毒性急性肺损伤肺组织MDA、SOD和IL-10、IL-18的改变[J].新生儿科杂志,2004,19(2):69-74
53.朱彩平,张声平.枸杞多糖对高脂血症小鼠血脂及脂质过氧化的影响[J].营养学报,2005,27(1):79-80
54.马荣英,任江平.复方丹参注射液治疗糖尿病肾病34例的临床观察[J].光明中医,2008(23):54-55
55. Navid E.Utility of the nitroblue tetrazolium reduction test for assessment of reactive oxygen species production by seminal leukocytes and spermatozoa[J].Andrology,2003,24:862-869
56. Yunbo L,Hong Z,Michael A.Detection of mitochondria-derived reactive oxygen speciesproduction by the chemilumigenic probes lucigenin and luminol[J].Biochimica et Bioph-ysica Acta,1999,1428:1-12
57.姚蜜林,张杰,汪涛,程惠娟.银翘玉屏风汤拮抗急性风寒应激小鼠免疫功能抑制作用实验研究[J].时珍国医国药,2001,1(12):97-99
58.张盈华,殷缨,张莉,郝晓柯,张利朝,邹爱民,陶秦渝.流式细胞仪测定巨噬细胞吞噬率方法的建立及其应用[J].第四军医大学学报,2002,23(17):1559-1561
59.张志强,田志刚,崔正言.MTT法检测NK和LAK活性的方法学探讨[J].中国实验临床免疫学杂志,1996,6(3):12-16
60. Jaeschke H.Reactive oxygen and mechanism of inflammatory liver injury[J].J Gas Hep 2000,15:718-724
61. Li N,Karin M.Is NF-kB the sensor of oxidative stress[J].Faseb,1999,13:1137-1143
62.段丽菊,王晓平,严彦.NO在甲醛介导的氧化损伤中的协同作用[J].环境科学学报,2006,26(3):505-508
63. Carrillo-Vico A,Lardone P J,Naji L,Fernandez-Santos J M,Martin-Laeave I,Guerrero JM,et a1.Beneftcial pleiotropic actions of melatonin in an experimental model of septic shoc k in mice:regulation of pro-/antiinflammatory cytokine network,protection against oxidative damage and anti-apoptotic efects[J].J PineaRes,2005,39(4):400-408
64. Garcia-Maurino S.Mecatonin enhances IL-2,IL-6,and IFN-gamms production by human-circulating CD4 cells:a possible nuclear receptor-med iatied mechanism involving The lpertype 1 lymphocytesand monocytes[J].J lmmunol,1997(2):574-581
65. Shaji AV,Kulkarni SK,Agrewala JN.Regulation of secretion of IL-4 and IgG1 isotype by melation-stimulated ovalbumin-specipic T cells[J].Clin Exp l-mmunol,1998,111(1):181-185
66. Kotler M,Rodriquez C,Sainz R M,et al.Melatonin increases gene expressionfor antioxid-ant enzymes in rat brain cortex[J].J Pineal Res,1998,24(2):83-89
67.陈微,陈晓峰.褪黑素对D-半乳糖大鼠记忆能力及大脑SOD、MDA的影响[J].中国民康医学,2009,62,(12):1338-1339
68. Navid E.Utility of the nitroblue tetrazolium reduction test for assessment ofreactive ox-ygen species production by seminal leukocytes and spermatozoa[J].Andrology,2003,24:862-869
69. Wang L,Zhou L,Tian R.Role of the area postrema of madulla oblongata in the regulation of canine interdigestive migarating motor complex[J].Chin Med J (Engl),2002,115(3) :384-388
70.郭继东,张晶等.褪黑素对脑缺血沙土海马MDA含量及SOD活性的影响[J].徐州医学院学报,2001,21(4):324-326
71. Singh S S,Haldar C,Rai S.Melatoninand diferential efect of Lthyruxine on immune system of Indian tropical bird Perdicula asiatica[J].Gen Comp Endocrinol,2006,145 (3):215-221
72.冯雪英,徐兆发等.原花青素和褪黑素对镉所致大鼠急性肝氧化损伤影响的实验研究[J].中国职业医学,2008,12(35):480-484
73.张超英,王辉等.褪黑素对低硒饲料大鼠肝脏损伤的影响[J].西安交通大学学报,2004,25(3):250-256
74. Jaeschke H.Reactive oxygen and mechanisms of inflammatory liver injury[J].J Gastroenterol Hepatol,2000,15(7):718-724
75. Rodriguez-Reynoso S,Leal C,Portilla E,et al.Effect of exogenous melatonin on hepatic energetic status during ischemia reperfuaion possible role of tu-mor necrosis factoalphaand nitric oxide[J].J Surg Res,2001,100(2):141-149
76. Jaeschke H.Molecular mechanisms of hepatic is chemia-reperfusion in injury and precond -itioning[J].Am J Physiol Gastrointest Liver Physiol,2003,284(1):G15-26
77. Bhain S,Singh A B,Javanbakht M.Neuroendocrine abnor malities associated with HIV infection[J].Endocrimol Metab Clim North Am,2001,30(3):749
78. Srinivasan V,Maestroni G,Cardinali D,Esquifino A,Perumalsp,MiUer S.Melatonin immu-ne function and aging[J].Immun Ageing,2005,2:17
79.刘泽源,徐贵丽,魏伟.褪黑素对海洛因依赖大鼠淋巴细胞增殖和IL-2产生的影响[J].中国药理学通报,2001,17(3):3192-3221
80. Baltaci AK,Mogulkoc R,Bediz CS,Pekel A.Effects of zinc deficiency and pinealectomyon cellular immunity in rats infected with Toxoplasma gondii[J].Biol Trace Elem Res,2005,104(1):47-56
81.周爱民,袁育康,范桂香,等.褪黑素的免疫调节作用[J].西安医科大学学报,2001,22(5):422-424
82. Reiter R J,Calvo J R,Karbownik M.Melatonin and its relation to the immune system and inflammation[J].Ann N Y Acad Sci,2000,917(2):376-386
83. Bhain S,Singh A B,Javanbakht M.Neuroendocrine abnormalities associated with HIV infection[J].Endocrinol Metab Clin North Am,2001,30(3):749
84.郑里,王淑仙,崔德玉等.介绍一种简便的炎症性肠疾病的评价方法[J].中国药理学通报,1996,12:468-469
85.崔利德,韩树斋等.褪黑素对大鼠脑缺血时MPO的活性和ICAM-1表达的影响[J].河北医科大学学报,2008,329(2):174-177
86.江秀秀,吕时铭.一氧化氮的抗感染作用研究进展[J].中国实验诊断学,2002,6:49-51
87. Hickey M J.Role of inducible nitric oxide synthase in the regulation of leucocyte rec-ruitment[J].Clin Sci(Lond),100,75:1-12
88. Colwman J W.Nitric oxide:a regulator of mast cell activation and mast cellmediated inflammation[J].Clin Exp Immunol,2002,129(1):4-10
89.赵红卫.一氧化氮与免疫调节[J].上海免疫学杂志,1996,16(6):373-377
90. Nguyen T,Brunson D,Crespi C L.DNA damage and mutation in human cells exposed to nitric-oxide in vitro[J].Proc Acid Sci USA,1992,99:303-310
91. Zemkova H,Vanecek J H J,Vanecek I.Inhibitory effect of melatonin on gonadotropinrele asi- ng hormone-induced Ca2+ oscillations in pituitary cells of newborn rats[J].Neuroendocrinol- ogy,1997,65(4):276-283
92. Tocharus,Jiraporn,Chongthammakun,et al.Melatonin inhibits amphetamine–indu- ced nitrico- xide synthase mRNA overexpression in microglial cell limes [J].Neuroscience Letters,200 8,439(2):134-137
93. Arand M,Melzner H,Kinzl L,et al.Early inflammatory mediator response follwing isolated traumatic brain injury and other major trauma in humans[J].Langenbecks Arch Sur- g,2001,386(4):241–248
94. Spittler A,Razenberger M,Kupper H,et al.Relationship between interleukin6 plasma concentr- ation in patients with sepsis monocyte phenotype,monoeyte phagocytic properties and cytoki- ne production[J].Clin Infect Dis,2000,31:1338-1420
95.慕宁,王海梁,傅宏,等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏[J].第二军医大学学报,2008,29(12):1429-1432.
96. Lakshminarayanan V,Drab-Weiss E A,Roebuck K A.H2O2 and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-kappaB to the interleukin8 promoter in endothelial and epithelial cells[J].J Bio-Chem, 1998,273(49):32670-3267854
97. Schwartz M D,Moore E E,Moore FA,et al.Nuclear factor-kappa B is activated in a lv-eolar macrophages from patients with acute respiratory distress sy-ndrome[J].Crit CareMed,1996,24(8):1285
98. Iszard M B,Liu J,Klaassen C D.Effect of several metallothionein inducers on oxidativestress defense mechanism in rats[J].Toxicology,1995,104(4):25-32
99. Cui L,Takagi Y,Wase M,et al.Zinc deficiency enhances interleukin-1α-induced metall- othionein-1 expression in rats[J].Nutr,1998,128:1092-1098
100. Lezoualch F,Sparapani M,behl C.N-acetyl-serotonin(normelatonin)and melatonin protect neurons against oxidative challenges and suppress the activity of the trans -cription factor NF-kappa B[J]. J Pineal Res,1998,24(3):168-178
101.杨文军,李德卫,时德.核因子-kB靶向性寡核苷酸“圈套”策略对创伤性炎症大鼠肝脏损伤的作用[J].中华实验外科杂志,2003,20:905-907
102.张万广,严斌,陈孝平.核因子-kB诱骗寡核苷酸增强阿霉素对肝癌耐药细胞化疗敏感性的机制[J].中华实验外科杂志,2006,23:1075-1078
103. Dunne A,Ejdeback M,Lndidi P L,et al.Structural complementarity of Toll Pinterl-eukin1- receptor domains in Toll-like receptors and adaptors Mal and MyD88[J].J Biol Chem,2003,278(42):41443-41451
104. Yamamoto M,Sato S,Hemmi H,et al.Role of adaptor TRIF in MyD88 independe- nt Toll-like receptor signaling pathway[J].Science,2003,301(5633):640-643
105. Del R L M,Quintanilla V B,Brambila C E,et al.Stress proteins induced by arsenic [J].Toxicol-Appl-Pharmacol,2001,177(2):132-148
106. Wong H R,Finder J D,Wasserloos K,et al. Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is inhibited by the heat shock response[J].Am J Physio -l,269:843-848
107. Wong HR,Ryan M,Gebb S,et al.Selective and transient in vitro sffects of heat shock on alveolar typeⅡcell gene expression[J].Am-J-Physiol,1997,272:132-138
108. De Vera M E,Wong J M,Zhou J Y,et al.Cytokine-induced nitric oxide synthase gene transcription in blocked by the heat shock response in human liver cells[J]. Surgery,1996,120 :144-149
109. Arnott C H,Scott K A,Moore R J,et al.Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha2 and AP-1-dependent pathway[J].Oncogene 200 -2,21(31):4728-4738
110. Royuela M,Rodrguez-Berriguete G,Fraile B,et al.TNF-alpha/IL-1/NF-kappaB transduction pathway in human cancer prostate[J].Histol Histopathol,2008,23(10) :1279-1290
111.殷咏梅,束永前等.TNF-α通过JNK和AP-1途径调节乳腺癌MCF-7细胞VEGF的表达[J].中国肿瘤生物资料杂志,2009,216(1) :12-17
2.魏涛,唐芬芳,金宗濂.褪黑素的生理功能[J].食品工业科技,2001,23(9):98-102
3.刘作易,梁宗琦.褪黑素的研究开发现状[J].生命化学,2001,21(1):69-70
4. Reiter R J.Remembrance:Growing up with the pineal gland[J].Endocrinol,1992,131 (5):2039-2041
5. Tan D X,Chen L D,Poeggeler B,et al.Melatonin:a potent,endogenous hydroxyl radical scavenger[J].Endocrinol J,1993,1(1):57-60
6. Russel J B,Dun X T,Carmen O,et al.Action of melatonin in the reduction of oxidation stress[J].Biomed Sci,2000,7(1):444-458
7. Reiter R,Tang L,Garcia J J ,et al.Pharma-cological actions of melatonin in oxygen radical pathophysiology[J].L ife Sci,1997,60(1):2255-2271
8. Hardeland R. Antioxidative protection by melatonin:multip licity of mechanisms from radical detoxification to radical avoidance[J].Endocrine,2005,27(2):119-130
9. Tomas-Zapico C,Coto-Montes A.A proposed mechanism to explain the stimulatory eff-ect of melatonin on antioxidative enzymes[J].J Pineal Res,2005,39(3):99-104
10. Hardeland R,Pandi-Perumal S R,Cardinali D P.Melatonin[J].Int J Biochem Cell Biol,20-06,38(3):313-316
11. Suzen S,Bozkaya P,Coban T,Nebiogu D.Investigation of the in vitro antioxidant behaviour of some 2-phenylindole derivatives: discussion on possible antioxidant mechanisms and compa- rison with melatonin[J].J Enzyme Inhib Med Chen ,2006,21(4):405-411
12. IanasO,Olnescu R,Badescu L.Melatonin involvement in oxidative stress[J].Rom J Endocrino- l,1991,29:147-153
13. Rriter R J,Tan D X,Poeggeler B, et al.Melatonin as a free radical scavenge: Imp lications for aging and age-related diseases[J].Ann NY Acad Sci,1994,719:1-12
14.陈泳宏,刘平.褪黑素在临床中的应用[J].中国临床康复,2003,7(4):654-655
15. Maharaj D S,Anoopkumar-Dukie S,Glass B D,et al.The identification of the UV degra-dants of melatonin and their ability to scavenge radicals[J].J Pineal Res,2002,32:257-261
16. Tomas-Zapico C,Coto-Montes A.A proposed mechanism to explain the stimulatory effe-ct of melatonin on antioxidative enzymes[J].J Pineal Res,2005,39(2):99-104
17. Tocharus,Jiraporn,Chongthammakun,et al.Melatonin inhibits amphetamine2 induced nitri-c oxide synthase mRNA overexp ression in microglial cell lines[J].NeuroscienceLetters,2008,439(2):134-137
18. OzdemirD,UysalN,Tugyan K,et al.The efect of melatonin on endo toxemia induced int-estinal apoptosis and oxidative stress in infant rats[J].Intensive CareMed,2007,33:63-84
19. Wang H,Wei W,Zhang S Y,et al.Melatonin-selenium nanoparticles inhibit oxidativestres-s and protect against hepatic injury induced by Bacillus Calmette2 Guerin/lipopolysaccharide in mice[J].J Pineal Reso,2005,39(2):156-163
20. Othman A I,al Sharawy S,el-Missiry M A.Role of melatonin in ameliorating lead indu-ced haematotoxicity[J].Pharmacol Res,2004,50(3):301-307
21. Oner H,Kus I,Oner J,Ogeturk M,Ozan E,Ayar A.Possible efects of melatonin on thym-us gland after pinealectomy in rats[J].Neum Endocrinol Lett,2004,25(1-2):115-118
22. Haldar C,SirIgh R.Pineal modulatin of thymus and immune function in aseasonallybreeding tropical rodent,Funambulus pennantic[J].J Exp Zool,2001,289(2):90-98
23. Brennan C P,Hedricks G L,EL-Sheikh T M,Mashaly M M.Melatonin and the enchan- cement of immune responses in immature male chickens[J].Pouh Sci,2002,81(3):371-375
24. Trubiani O,Recchioni R,Moroni F,Pizzicannella J,Caputi S,Di Primio R. Melatonin pro-vokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pat-hway activation[J].J Pineal Res,2005,39(4):425–431
25. Maestroni G J.Eimmunotherapeutic potential of melatonin[J].Export Opin-lnvestig Drug-s,2001,10(3):467-476
26. Negrette B,Bonilla E,Valero N,Pons H,Garcia Tamayo J,Chacin Bonilla L,eta1.Melatoni-n treatment enhances the efficiency of mice immunization with Vnezuelan equine enc-ephalomyelitis virus TC-83[J].Neurochem Res,2001,26(7):767-770
27. Akbuut K G,Gonul B,Akbuut H.The efects of melatonin on humoral immune responses of young and aged rats[J].1mmunol Invest,2001,30(1):17-20
28. Baltaci AK,Mogulkoc R,Bediz CS,Pekel A.Efects of zinc deftciency and pinealectomy on cellular immunity in rats infected with Toxoplasma gondii[J].Biol Trace Elem Res,2005,104(1):47-56
29. Litvinenko G I,Shurlygina A V,Verbitskaya L V,Panteleeva N G,Melnikova E V,Trufakin V A. Circadian dynamics of cell composition of the thymus an d lymph nodes in mice normally,under conditions of permanent illumination,and after melatonin injection[J].Bull Exp Biol Med,2005,140(2):213-216
30. HuangY S,Jiang J W,Wu G C,Cao X D.Effect of melatonin and electro acupuncture (EA) on NK cell activity,interleukin-2 prduction and POMC derived peptides in traumatic rats[J].Acapunct Electrotller Res,2002,27(2):95-105
31. Srinivasan V,Maestroni G,Cardinali D,Esquifino A,Perumal SP,MiUer S.Mel-atonin,immune function and aglng[J]Lmmun Ageing,2005,2:17
32. Arias J,Melean E,Valero N,Pons H,Chacin-Bonilla L,Larreal Y,et a1. Efect of melatonin on lymphocyte proliferation an d production of interleukin-2(IL-2)and interleukin-l beta(IL-lbeta) in mice splenocytes[J].Invest Clin,2003,44(1):41-50
33. Carrillo-Vico A,Lardone P J,Naji L,Fernandez-Santos J M,Martin-Laeave I,Guerrero J M,et a1.Beneftcial pleiotropic actions of melatonin in an experi-mental model of septi-c shock in mice:regulation of pro-/antiinflammatory c-ytokine network,protection agains-t oxidative damage and anti-apoptotic efec-ts[J].J PineaRes,2005,39(4):400-408
34. Garcia-Maurino S.Mecatonin enhances IL-2,IL-6,and IFN-gamms production by humancirculating CD4 cells,a possible nuclear receptor-med iatied mechanism involving Thel-per type 1 lymphocytesand monocytes[J].J lmmunol,1997,159(2):574-581
35. Shaji A V,Kulkarni S K,Agrewala J N.Regulation of secretion of IL-4 and IgG1 isoty-pe by melation-stimulated ovalbumin-specipic T cells[J].Clin Exp lmmunol,1998,111(1):181-185
36. Dimitrov S,Lange T,Tieken S,Fehm H L,Born J. Sleep associated regulationof T helpe-r 1/T helper 2 cytokine balance in humans[J].Brain Behav lmmun,2004,18(5):341-348
37. Rodriguez-Iturbe B,Zhan C D,Quiroz Y,et al.Antioxidant-rish diet relieves hypertensionand reduces renal immune infiltration in spontaneously hypertensive rat [J].Hypertensio-n,2003,41(2):341-346
38. Stolk J,Seersholm N,Kalsheker N.Alphal-antitrypsin deficiency current perspective on research,diagnosis,and management[J].Chron Obstruct Pulmon Dis,2006, 1(2):151-160
39. May M J,Ghosh S.Signal transduction through NF-kappa B[J].Immunol Today,1998,19:80-88
40. Savill J.Apoptosis in resolution of inflammation[J].Journal of Leucocyte Biology,1997,61(4):375-380
41.慕宁,王海梁,傅宏,等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏[J].第二军医大学学报,2008,29(12):1429-1432
42. Lakshminarayanan V,Drab-Weiss E A,Roebuck K A.H2O2 and tumor necrosis factoralp-ha induce differential binding of the redox-responsive transcription factors AP-1and NF-kappaB to the interleukin-8 promoter in endothelialand epithelial cells[J].J Bio Chem,1998,273(49):32670-32678
43.李振,蔡小嫦.Th1/Th2细胞在炎症浸润中的不同表现[J].国外医学免疫学分册,2002,25(1):36-38
44. Zabel U,Henkel T,Silva M S,et al.Nuclear uptake control of NF-kappaB by MAD-3,and NF-kappaB protein present in the nucleus[J].EMBO J ,1993,12:201-211
45. Bloomfield G L,Holloway S,Ridings P C,et al.Pretreatment with inhaled nitric oxide inhibits neutrophil migration and oxidative activity resulting in attenuated sepsis-induce-d acute lung injury[J].Crit Care Med,1997,25:584-593
46.吴惠,杨向红,董玉兰,等.脂质过氧化对人血管内皮细胞NO合成的影响及维生素E的作用[J].中华病理学杂志,2002,31:260-261
47.胡文秀,杨成旺.大肠癌组织中HSP70和p53蛋白的表达及其意义[J].肿瘤防治研究,2007,5:363-365
48.傅庆国,孟凡东,郭克建,等.热休克蛋白70在诱导肿瘤免疫中的效应[J].中华微生物学和免疫学杂志,2003,23(1):31-33
49.黄晓兵,候梅.热休克蛋白与肿瘤细胞凋亡[J].四川肿瘤防治,2003,16(1):53-55
50. Arnott C H,Scott K A,Moore R J,et a1.Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha-and AP-1-dependent pathway[J].Oncogene,2002,21(31):4728-47 38
51. Chinenov Y,Kerppola T K.Close encounters of many kinds:Fos-Jun interactions that mediate transcrip tion regulatory specificity[J].Oncogene,2001,20(19):2438-2452
52.董淑红,苏力,魏克伦等.新生大鼠内毒性急性肺损伤肺组织MDA、SOD和IL-10、IL-18的改变[J].新生儿科杂志,2004,19(2):69-74
53.朱彩平,张声平.枸杞多糖对高脂血症小鼠血脂及脂质过氧化的影响[J].营养学报,2005,27(1):79-80
54.马荣英,任江平.复方丹参注射液治疗糖尿病肾病34例的临床观察[J].光明中医,2008(23):54-55
55. Navid E.Utility of the nitroblue tetrazolium reduction test for assessment of reactive oxygen species production by seminal leukocytes and spermatozoa[J].Andrology,2003,24:862-869
56. Yunbo L,Hong Z,Michael A.Detection of mitochondria-derived reactive oxygen speciesproduction by the chemilumigenic probes lucigenin and luminol[J].Biochimica et Bioph-ysica Acta,1999,1428:1-12
57.姚蜜林,张杰,汪涛,程惠娟.银翘玉屏风汤拮抗急性风寒应激小鼠免疫功能抑制作用实验研究[J].时珍国医国药,2001,1(12):97-99
58.张盈华,殷缨,张莉,郝晓柯,张利朝,邹爱民,陶秦渝.流式细胞仪测定巨噬细胞吞噬率方法的建立及其应用[J].第四军医大学学报,2002,23(17):1559-1561
59.张志强,田志刚,崔正言.MTT法检测NK和LAK活性的方法学探讨[J].中国实验临床免疫学杂志,1996,6(3):12-16
60. Jaeschke H.Reactive oxygen and mechanism of inflammatory liver injury[J].J Gas Hep 2000,15:718-724
61. Li N,Karin M.Is NF-kB the sensor of oxidative stress[J].Faseb,1999,13:1137-1143
62.段丽菊,王晓平,严彦.NO在甲醛介导的氧化损伤中的协同作用[J].环境科学学报,2006,26(3):505-508
63. Carrillo-Vico A,Lardone P J,Naji L,Fernandez-Santos J M,Martin-Laeave I,Guerrero JM,et a1.Beneftcial pleiotropic actions of melatonin in an experimental model of septic shoc k in mice:regulation of pro-/antiinflammatory cytokine network,protection against oxidative damage and anti-apoptotic efects[J].J PineaRes,2005,39(4):400-408
64. Garcia-Maurino S.Mecatonin enhances IL-2,IL-6,and IFN-gamms production by human-circulating CD4 cells:a possible nuclear receptor-med iatied mechanism involving The lpertype 1 lymphocytesand monocytes[J].J lmmunol,1997(2):574-581
65. Shaji AV,Kulkarni SK,Agrewala JN.Regulation of secretion of IL-4 and IgG1 isotype by melation-stimulated ovalbumin-specipic T cells[J].Clin Exp l-mmunol,1998,111(1):181-185
66. Kotler M,Rodriquez C,Sainz R M,et al.Melatonin increases gene expressionfor antioxid-ant enzymes in rat brain cortex[J].J Pineal Res,1998,24(2):83-89
67.陈微,陈晓峰.褪黑素对D-半乳糖大鼠记忆能力及大脑SOD、MDA的影响[J].中国民康医学,2009,62,(12):1338-1339
68. Navid E.Utility of the nitroblue tetrazolium reduction test for assessment ofreactive ox-ygen species production by seminal leukocytes and spermatozoa[J].Andrology,2003,24:862-869
69. Wang L,Zhou L,Tian R.Role of the area postrema of madulla oblongata in the regulation of canine interdigestive migarating motor complex[J].Chin Med J (Engl),2002,115(3) :384-388
70.郭继东,张晶等.褪黑素对脑缺血沙土海马MDA含量及SOD活性的影响[J].徐州医学院学报,2001,21(4):324-326
71. Singh S S,Haldar C,Rai S.Melatoninand diferential efect of Lthyruxine on immune system of Indian tropical bird Perdicula asiatica[J].Gen Comp Endocrinol,2006,145 (3):215-221
72.冯雪英,徐兆发等.原花青素和褪黑素对镉所致大鼠急性肝氧化损伤影响的实验研究[J].中国职业医学,2008,12(35):480-484
73.张超英,王辉等.褪黑素对低硒饲料大鼠肝脏损伤的影响[J].西安交通大学学报,2004,25(3):250-256
74. Jaeschke H.Reactive oxygen and mechanisms of inflammatory liver injury[J].J Gastroenterol Hepatol,2000,15(7):718-724
75. Rodriguez-Reynoso S,Leal C,Portilla E,et al.Effect of exogenous melatonin on hepatic energetic status during ischemia reperfuaion possible role of tu-mor necrosis factoalphaand nitric oxide[J].J Surg Res,2001,100(2):141-149
76. Jaeschke H.Molecular mechanisms of hepatic is chemia-reperfusion in injury and precond -itioning[J].Am J Physiol Gastrointest Liver Physiol,2003,284(1):G15-26
77. Bhain S,Singh A B,Javanbakht M.Neuroendocrine abnor malities associated with HIV infection[J].Endocrimol Metab Clim North Am,2001,30(3):749
78. Srinivasan V,Maestroni G,Cardinali D,Esquifino A,Perumalsp,MiUer S.Melatonin immu-ne function and aging[J].Immun Ageing,2005,2:17
79.刘泽源,徐贵丽,魏伟.褪黑素对海洛因依赖大鼠淋巴细胞增殖和IL-2产生的影响[J].中国药理学通报,2001,17(3):3192-3221
80. Baltaci AK,Mogulkoc R,Bediz CS,Pekel A.Effects of zinc deficiency and pinealectomyon cellular immunity in rats infected with Toxoplasma gondii[J].Biol Trace Elem Res,2005,104(1):47-56
81.周爱民,袁育康,范桂香,等.褪黑素的免疫调节作用[J].西安医科大学学报,2001,22(5):422-424
82. Reiter R J,Calvo J R,Karbownik M.Melatonin and its relation to the immune system and inflammation[J].Ann N Y Acad Sci,2000,917(2):376-386
83. Bhain S,Singh A B,Javanbakht M.Neuroendocrine abnormalities associated with HIV infection[J].Endocrinol Metab Clin North Am,2001,30(3):749
84.郑里,王淑仙,崔德玉等.介绍一种简便的炎症性肠疾病的评价方法[J].中国药理学通报,1996,12:468-469
85.崔利德,韩树斋等.褪黑素对大鼠脑缺血时MPO的活性和ICAM-1表达的影响[J].河北医科大学学报,2008,329(2):174-177
86.江秀秀,吕时铭.一氧化氮的抗感染作用研究进展[J].中国实验诊断学,2002,6:49-51
87. Hickey M J.Role of inducible nitric oxide synthase in the regulation of leucocyte rec-ruitment[J].Clin Sci(Lond),100,75:1-12
88. Colwman J W.Nitric oxide:a regulator of mast cell activation and mast cellmediated inflammation[J].Clin Exp Immunol,2002,129(1):4-10
89.赵红卫.一氧化氮与免疫调节[J].上海免疫学杂志,1996,16(6):373-377
90. Nguyen T,Brunson D,Crespi C L.DNA damage and mutation in human cells exposed to nitric-oxide in vitro[J].Proc Acid Sci USA,1992,99:303-310
91. Zemkova H,Vanecek J H J,Vanecek I.Inhibitory effect of melatonin on gonadotropinrele asi- ng hormone-induced Ca2+ oscillations in pituitary cells of newborn rats[J].Neuroendocrinol- ogy,1997,65(4):276-283
92. Tocharus,Jiraporn,Chongthammakun,et al.Melatonin inhibits amphetamine–indu- ced nitrico- xide synthase mRNA overexpression in microglial cell limes [J].Neuroscience Letters,200 8,439(2):134-137
93. Arand M,Melzner H,Kinzl L,et al.Early inflammatory mediator response follwing isolated traumatic brain injury and other major trauma in humans[J].Langenbecks Arch Sur- g,2001,386(4):241–248
94. Spittler A,Razenberger M,Kupper H,et al.Relationship between interleukin6 plasma concentr- ation in patients with sepsis monocyte phenotype,monoeyte phagocytic properties and cytoki- ne production[J].Clin Infect Dis,2000,31:1338-1420
95.慕宁,王海梁,傅宏,等.落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏[J].第二军医大学学报,2008,29(12):1429-1432.
96. Lakshminarayanan V,Drab-Weiss E A,Roebuck K A.H2O2 and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-kappaB to the interleukin8 promoter in endothelial and epithelial cells[J].J Bio-Chem, 1998,273(49):32670-3267854
97. Schwartz M D,Moore E E,Moore FA,et al.Nuclear factor-kappa B is activated in a lv-eolar macrophages from patients with acute respiratory distress sy-ndrome[J].Crit CareMed,1996,24(8):1285
98. Iszard M B,Liu J,Klaassen C D.Effect of several metallothionein inducers on oxidativestress defense mechanism in rats[J].Toxicology,1995,104(4):25-32
99. Cui L,Takagi Y,Wase M,et al.Zinc deficiency enhances interleukin-1α-induced metall- othionein-1 expression in rats[J].Nutr,1998,128:1092-1098
100. Lezoualch F,Sparapani M,behl C.N-acetyl-serotonin(normelatonin)and melatonin protect neurons against oxidative challenges and suppress the activity of the trans -cription factor NF-kappa B[J]. J Pineal Res,1998,24(3):168-178
101.杨文军,李德卫,时德.核因子-kB靶向性寡核苷酸“圈套”策略对创伤性炎症大鼠肝脏损伤的作用[J].中华实验外科杂志,2003,20:905-907
102.张万广,严斌,陈孝平.核因子-kB诱骗寡核苷酸增强阿霉素对肝癌耐药细胞化疗敏感性的机制[J].中华实验外科杂志,2006,23:1075-1078
103. Dunne A,Ejdeback M,Lndidi P L,et al.Structural complementarity of Toll Pinterl-eukin1- receptor domains in Toll-like receptors and adaptors Mal and MyD88[J].J Biol Chem,2003,278(42):41443-41451
104. Yamamoto M,Sato S,Hemmi H,et al.Role of adaptor TRIF in MyD88 independe- nt Toll-like receptor signaling pathway[J].Science,2003,301(5633):640-643
105. Del R L M,Quintanilla V B,Brambila C E,et al.Stress proteins induced by arsenic [J].Toxicol-Appl-Pharmacol,2001,177(2):132-148
106. Wong H R,Finder J D,Wasserloos K,et al. Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is inhibited by the heat shock response[J].Am J Physio -l,269:843-848
107. Wong HR,Ryan M,Gebb S,et al.Selective and transient in vitro sffects of heat shock on alveolar typeⅡcell gene expression[J].Am-J-Physiol,1997,272:132-138
108. De Vera M E,Wong J M,Zhou J Y,et al.Cytokine-induced nitric oxide synthase gene transcription in blocked by the heat shock response in human liver cells[J]. Surgery,1996,120 :144-149
109. Arnott C H,Scott K A,Moore R J,et al.Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha2 and AP-1-dependent pathway[J].Oncogene 200 -2,21(31):4728-4738
110. Royuela M,Rodrguez-Berriguete G,Fraile B,et al.TNF-alpha/IL-1/NF-kappaB transduction pathway in human cancer prostate[J].Histol Histopathol,2008,23(10) :1279-1290
111.殷咏梅,束永前等.TNF-α通过JNK和AP-1途径调节乳腺癌MCF-7细胞VEGF的表达[J].中国肿瘤生物资料杂志,2009,216(1) :12-17