一氧化氮与炎症性关节疾病
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资料包括： 论文(6页4453字)
说明：
关键词： 一氧化氮(NO), 关节疾病,炎症
一氧化氮(nitric oxide,NO)是由L-精氨酸(L-arginine，L-Arg)胍基氮经NO合酶(NO synthase，NOS)的催化发生氧化而形成。NO既兼有第二信使和神经递质的功能，又是效应分子，介导和调节多种生理和病理过程〔1，2〕。Stadler等〔3〕于1991年用白介素1(interleukin 1，IL-1)或内毒素诱导软骨细胞合成NO，提供了软骨代谢涉及NO的最早证据。1992年Farrell等〔4〕发现在类风湿关节炎(rheumatoid arthritis，RA)和骨关节炎(osteoarthritis，OA)病人的滑膜液和血清中可检测到大量NO代谢产物亚硝酸盐(nitrite，NO－2)，推测NO可能参与这二种疾病关节炎症的病理过程。以后诸多学者〔5，6〕使用NOS抑制剂等工具药对多种关节炎动物模型进行了研究，证实NO是这些关节炎发病过程中的一种重要炎症介质，由此推动了NO与炎症性关节疾病关系的深入研究。本文就NO涉及炎症性关节疾病以及有关药物治疗方面的进展作一综述。
1 NO参与炎症性关节疾病的发病过程
1.1 关节炎病人：RA和OA滑膜液或血清中NO－2含量以及尿中硝酸盐(nitrate，NO－3)或NO－2/NO－3排出量均高于正常人〔4，7～9〕。强的松龙0.5 mg/kg口服，连续2～4周，不但降低RA患者C反应蛋白、血沉、晨僵时间与关节疼痛指数，而且还明显减少尿中NO－3排出。给活动期RA患者甲基强的松龙冲击治疗，1 g/d，连续3天，第4天患者滑膜液中S-亚硝基蛋白(S-nitrosoproteins，S-NP)含量明显减少，且与患者症状、体征以及实验室指标改善呈明显正相关，表明NO可能参与炎症性关节疾病的发病过程。
目录：
1 NO参与炎症性关节疾病的发病过程
2 NO参与炎症关节损伤的作用机制
3 药物对NO产生的调控作用
4 问题与展望
参考文献：
1 陈敏珠.一氧化氮与炎症免疫细胞.中国药理学通报，1992，8(6)：409-415
2 Cllancy RM,Amin AR,Abramson SB.The role of nitric oxide in inflammation and immunity.Arthritis Rheum,1998,41:1141-1151
3 Stadler J,Stefanovic-racic M,Billiar T,et al.Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide.J Immunol,1991,147:3915-3920
4 Farrell A,Blake D,Palmer R,et al.Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.Ann Rheum Dis,1992,51:1219-1222
5 Stefanovic-Racic M,Stadler J,Evans CH.Nitric oxide and arthritis.Arthritis Rheum,1993,36:1036-1044
6 Stefanovic-Racic M,Meyers K,Meschter C,et al.N-monomethyl arginine,an inhibitor of nitric oxide synthase,suppesses the development of adjuvant arthritis in rats.Arthritis Rheum,1994,37:1062-1069
7 Stichtenoth DO,Fauler J,Zeidler H,et al.Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.Ann Rheum Dis,1995,54:820-824
8 Grabowski PS,England AJ,Dykhuizen R,et al.Elevated nitric oxide production in rheumatoid arthritis.Arthritis Rheum,1996,39:643-647
9 Borderie PHD,Hernvann A,Menkes CJ,et al.Nitric oxide as s-nitrosoproteins in rheumatoid arthritis.Arthritis Rheum,1997,40:1512-1517
10 Cannon G,Openshaw S,Hibbs JB,et al.Nitric oxide production during adjuvant-induced and collagen-induced arthritis.Arthritis Rheum,1996,39:1677-1684
11 Wei XQ,Charles IG,Smith A,et al.Altered immune responses in mice lacking inducible nitric oxide synthase.Nature,1995,375:408-411
12 王斌，周爱武，陈敏珠.一氧化氮参与炎症性关节损伤的过程.中国药理学通讯，1998，15：37
13 Salvemini D,Manning PT,Zweifel BS,et al.Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors.J Clin Invest,1995,96:301-308
14 Francisco JB,Martin L.IL-1-induced nitric oxide inhibits chondrrocyte proliferation via PGE2.Exp Cell Res,1995,218:319-325
15 Stefanovic-racic M,stadler J,Georgescu HI,et al.Nitric oxide synthesis and its regulation by rabbit synoviocyte.J Rheumatol,1994,21:1892-1897
16 McInnes BB,Leung BP,Field M,et al.Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients.J Exp Med,1996,184:1519-1524
17 Marcinkiewicz J,Grabowska A,Chain B.Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages.Eur J Immunol,1995,25:947-951
18 Murrell GAC,Jang D,Williams RJ.Nitric oxide activates metalloprotease enzymes in articular cartilage.Biochem Biophys Res Commun,1995,206:15-21
19 Salvemini D,Zhi-Qiang W,Wyatt PS,et al.Nitric oxide:a key mediator in the early and late phase of carrageenan-induced rat paw inflammation.Br J Pharmcol,1996,118:829-838
20 王斌，姚余有，周爱武，等.白芍总甙对佐剂性关节炎大鼠的免疫调节作用及其与一氧化氮的研究.中国免疫学杂志，1996，12：104-106
21 Amin AR,Cesare PED,Vyas P,et al.The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes:evidence for Up-regulated neuronal nitric oxide synthase.J Exp Med,1995,182:2097-2102
22 Amin AR,Vyas P,Attur M,et al.The mode of action of aspirin-like drugs:Effect on inducible nitric oxide synthase.Proc Natl Acad Sci USA,1995,92:7926-7930
23 Kwon NS,Nathan CF,Stuehr DJ.Reduced biopterin as a cofactor in the generation of nitrogen oxides by murin macrophages.J Biol Chem,1989,264:20496-20501
24 Amin AR,Attur MG,Thakker GD,et al.A novel mechanism of action of tetracyclines:effects on nitric oxide synthases.Proc Natl Acad Sci USA,1996,93:14014-14019
25 Miesel R,Ehrlich W,Wohlert H,et al.The effects of interleukin-1 receptor antagonist on oxidant-induced arthritis in mice.Clin Exp Rheumatol,1995,13:595-601
26 王斌，姚余有，周爱武，等.白芍总甙对佐剂性关节炎大鼠关节损伤的保护作用.中国药理学与毒理学杂志，1996，10：211-214
27 Kaur H,Halliwell B.Evidence for nitric oxide-mediated damage in chronic inflammation:Nitrotyrosine in serum and synovial fluid from rheumatoid patients.FEBS Lett,1994,350:9-12
28 Wigand R,Meyer J,Busse R,et al.Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as index of an increased nitric oxide synthase activity.Ann Rheum Dis,1997,56:330-332
29 Aupperle KR,Boyle DL,Hendrix M,et al.Regulation of synoviocyte proliferation,apoptosis,and invasion by the p53 tumor suppression gene.Am J Pathol,1998,152:1091-1097
资料包括： 论文(6页4453字)
说明：
关键词： 一氧化氮(NO), 关节疾病,炎症
一氧化氮(nitric oxide,NO)是由L-精氨酸(L-arginine，L-Arg)胍基氮经NO合酶(NO synthase，NOS)的催化发生氧化而形成。NO既兼有第二信使和神经递质的功能，又是效应分子，介导和调节多种生理和病理过程〔1，2〕。Stadler等〔3〕于1991年用白介素1(interleukin 1，IL-1)或内毒素诱导软骨细胞合成NO，提供了软骨代谢涉及NO的最早证据。1992年Farrell等〔4〕发现在类风湿关节炎(rheumatoid arthritis，RA)和骨关节炎(osteoarthritis，OA)病人的滑膜液和血清中可检测到大量NO代谢产物亚硝酸盐(nitrite，NO－2)，推测NO可能参与这二种疾病关节炎症的病理过程。以后诸多学者〔5，6〕使用NOS抑制剂等工具药对多种关节炎动物模型进行了研究，证实NO是这些关节炎发病过程中的一种重要炎症介质，由此推动了NO与炎症性关节疾病关系的深入研究。本文就NO涉及炎症性关节疾病以及有关药物治疗方面的进展作一综述。
1 NO参与炎症性关节疾病的发病过程
1.1 关节炎病人：RA和OA滑膜液或血清中NO－2含量以及尿中硝酸盐(nitrate，NO－3)或NO－2/NO－3排出量均高于正常人〔4，7～9〕。强的松龙0.5 mg/kg口服，连续2～4周，不但降低RA患者C反应蛋白、血沉、晨僵时间与关节疼痛指数，而且还明显减少尿中NO－3排出。给活动期RA患者甲基强的松龙冲击治疗，1 g/d，连续3天，第4天患者滑膜液中S-亚硝基蛋白(S-nitrosoproteins，S-NP)含量明显减少，且与患者症状、体征以及实验室指标改善呈明显正相关，表明NO可能参与炎症性关节疾病的发病过程。
目录：
1 NO参与炎症性关节疾病的发病过程
2 NO参与炎症关节损伤的作用机制
3 药物对NO产生的调控作用
4 问题与展望
参考文献：
1 陈敏珠.一氧化氮与炎症免疫细胞.中国药理学通报，1992，8(6)：409-415
2 Cllancy RM,Amin AR,Abramson SB.The role of nitric oxide in inflammation and immunity.Arthritis Rheum,1998,41:1141-1151
3 Stadler J,Stefanovic-racic M,Billiar T,et al.Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide.J Immunol,1991,147:3915-3920
4 Farrell A,Blake D,Palmer R,et al.Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.Ann Rheum Dis,1992,51:1219-1222
5 Stefanovic-Racic M,Stadler J,Evans CH.Nitric oxide and arthritis.Arthritis Rheum,1993,36:1036-1044
6 Stefanovic-Racic M,Meyers K,Meschter C,et al.N-monomethyl arginine,an inhibitor of nitric oxide synthase,suppesses the development of adjuvant arthritis in rats.Arthritis Rheum,1994,37:1062-1069
7 Stichtenoth DO,Fauler J,Zeidler H,et al.Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.Ann Rheum Dis,1995,54:820-824
8 Grabowski PS,England AJ,Dykhuizen R,et al.Elevated nitric oxide production in rheumatoid arthritis.Arthritis Rheum,1996,39:643-647
9 Borderie PHD,Hernvann A,Menkes CJ,et al.Nitric oxide as s-nitrosoproteins in rheumatoid arthritis.Arthritis Rheum,1997,40:1512-1517
10 Cannon G,Openshaw S,Hibbs JB,et al.Nitric oxide production during adjuvant-induced and collagen-induced arthritis.Arthritis Rheum,1996,39:1677-1684
11 Wei XQ,Charles IG,Smith A,et al.Altered immune responses in mice lacking inducible nitric oxide synthase.Nature,1995,375:408-411
12 王斌，周爱武，陈敏珠.一氧化氮参与炎症性关节损伤的过程.中国药理学通讯，1998，15：37
13 Salvemini D,Manning PT,Zweifel BS,et al.Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors.J Clin Invest,1995,96:301-308
14 Francisco JB,Martin L.IL-1-induced nitric oxide inhibits chondrrocyte proliferation via PGE2.Exp Cell Res,1995,218:319-325
15 Stefanovic-racic M,stadler J,Georgescu HI,et al.Nitric oxide synthesis and its regulation by rabbit synoviocyte.J Rheumatol,1994,21:1892-1897
16 McInnes BB,Leung BP,Field M,et al.Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients.J Exp Med,1996,184:1519-1524
17 Marcinkiewicz J,Grabowska A,Chain B.Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages.Eur J Immunol,1995,25:947-951
18 Murrell GAC,Jang D,Williams RJ.Nitric oxide activates metalloprotease enzymes in articular cartilage.Biochem Biophys Res Commun,1995,206:15-21
19 Salvemini D,Zhi-Qiang W,Wyatt PS,et al.Nitric oxide:a key mediator in the early and late phase of carrageenan-induced rat paw inflammation.Br J Pharmcol,1996,118:829-838
20 王斌，姚余有，周爱武，等.白芍总甙对佐剂性关节炎大鼠的免疫调节作用及其与一氧化氮的研究.中国免疫学杂志，1996，12：104-106
21 Amin AR,Cesare PED,Vyas P,et al.The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes:evidence for Up-regulated neuronal nitric oxide synthase.J Exp Med,1995,182:2097-2102
22 Amin AR,Vyas P,Attur M,et al.The mode of action of aspirin-like drugs:Effect on inducible nitric oxide synthase.Proc Natl Acad Sci USA,1995,92:7926-7930
23 Kwon NS,Nathan CF,Stuehr DJ.Reduced biopterin as a cofactor in the generation of nitrogen oxides by murin macrophages.J Biol Chem,1989,264:20496-20501
24 Amin AR,Attur MG,Thakker GD,et al.A novel mechanism of action of tetracyclines:effects on nitric oxide synthases.Proc Natl Acad Sci USA,1996,93:14014-14019
25 Miesel R,Ehrlich W,Wohlert H,et al.The effects of interleukin-1 receptor antagonist on oxidant-induced arthritis in mice.Clin Exp Rheumatol,1995,13:595-601
26 王斌，姚余有，周爱武，等.白芍总甙对佐剂性关节炎大鼠关节损伤的保护作用.中国药理学与毒理学杂志，1996，10：211-214
27 Kaur H,Halliwell B.Evidence for nitric oxide-mediated damage in chronic inflammation:Nitrotyrosine in serum and synovial fluid from rheumatoid patients.FEBS Lett,1994,350:9-12
28 Wigand R,Meyer J,Busse R,et al.Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as index of an increased nitric oxide synthase activity.Ann Rheum Dis,1997,56:330-332
29 Aupperle KR,Boyle DL,Hendrix M,et al.Regulation of synoviocyte proliferation,apoptosis,and invasion by the p53 tumor suppression gene.Am J Pathol,1998,152:1091-1097