妊娠期高血压疾病患者血清中TNF-α和IL-10水平及其意义
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摘要
目的:观察妊娠期高血压疾病患者血清中Th1型细胞因子(TNF-α)和Th2型细胞因子(IL-10)水平,以及Th1/Th2(TNF-α/IL-10)比值的变化,探讨上述指标在妊娠期高血压疾病发病中的意义。
方法:采用ABC-ELISA法测定64例妊娠期高血压疾病患者(其中22例妊娠期高血压组;24例子痫前期组;18例子痫组);25例正常对照组血清中TNF-α和IL-10的水平,并计算Th1/Th2(TNF-α/IL-10)比值;比较各组间细胞因子水平及Th1/Th2比值的差异。
结果:①与对照组相比较,妊娠高血压组TNF-α水平无显著差异,(p＞0.05);子痫前期组及子痫组TNF-α水平均有极显著差异,(p＜0.001),且随病情加重而呈逐渐增加趋势。②妊娠高血压疾病患者血清中IL-10水平随病情加重而呈下降趋势,其中妊娠高血压组无显著差异(p＞0.05);子痫前期组及子痫组IL-10水平均有极显著差异(p＜0.001)。③与正常对照组相比较,妊娠高血压组TNF-α/IL-10比值无显著差异,(p＞0.05);子痫前期组及子痫组TNF-α/IL-10比值均有显著差异,(p＜0.001)。
结论:妊娠期高血压疾病患者Th1型细胞因子TNF-α表达增加,而Th2型细胞因子IL-10表达下降,Th1/Th2比值显著增高。说明妊娠期高血压疾病患者存在着免疫失衡,细胞因子TNF-α和IL-10水平以及TNF-α/IL-10的平衡改变是其重要的病理生理变化之一,可能与妊娠期高血压疾病的发生、发展有关。
Objective: To investigate the changes in serum levels of Th1-type cytokines (TNF-α) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 ( TNF-α/IL-10) in gestational hypertension. Methods: IL-10 and TNF-αwere determined with ABC-ELISA in serum samples from 22 women with gestational hypertension, 24 women with preeclampsia, 18 women with eclampsia and 25 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly. Results: There were no significant differences in serum levels of IL-10 and TNF-α(P> 0. 05 for all) among normal pregnancy and gestational hypertension . There were significant differences in serum levels of IL-10 and TNF-α( p < 0.001 for all) among preeclampsia and eclampsia. The ratio of serum TNF-α/ IL-10 was no significantly higher among normal pregnancy and gestational hypertension (P>0.05), and the ratio of TNF-α/IL-10 significantly higher in patients with preeclampsia and eclampsia than that in either controls or gestational hypertension (P<0.001) .Conclusion: Gestational hypertension patients Th1-type cytokines TNF-αexpression increased, while Th2 cytokine IL-10 expression decline, Th1/Th2 ratio was significantly higher. Th1 / Th2 cytokines to the balance of Th1 migration, that is, enhance the functions of Th1 cells, decrease the functions of Th2 cells. Alterations of serum cytokine balance with predominance of Th1 immunity were observed in hypertensive disorder complicating pregnancy. These associations may offer insight into the pathogenesis of hypertensive disorder complicating pregnancy.
方法:采用ABC-ELISA法测定64例妊娠期高血压疾病患者(其中22例妊娠期高血压组;24例子痫前期组;18例子痫组);25例正常对照组血清中TNF-α和IL-10的水平,并计算Th1/Th2(TNF-α/IL-10)比值;比较各组间细胞因子水平及Th1/Th2比值的差异。
结果:①与对照组相比较,妊娠高血压组TNF-α水平无显著差异,(p＞0.05);子痫前期组及子痫组TNF-α水平均有极显著差异,(p＜0.001),且随病情加重而呈逐渐增加趋势。②妊娠高血压疾病患者血清中IL-10水平随病情加重而呈下降趋势,其中妊娠高血压组无显著差异(p＞0.05);子痫前期组及子痫组IL-10水平均有极显著差异(p＜0.001)。③与正常对照组相比较,妊娠高血压组TNF-α/IL-10比值无显著差异,(p＞0.05);子痫前期组及子痫组TNF-α/IL-10比值均有显著差异,(p＜0.001)。
结论:妊娠期高血压疾病患者Th1型细胞因子TNF-α表达增加,而Th2型细胞因子IL-10表达下降,Th1/Th2比值显著增高。说明妊娠期高血压疾病患者存在着免疫失衡,细胞因子TNF-α和IL-10水平以及TNF-α/IL-10的平衡改变是其重要的病理生理变化之一,可能与妊娠期高血压疾病的发生、发展有关。
Objective: To investigate the changes in serum levels of Th1-type cytokines (TNF-α) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 ( TNF-α/IL-10) in gestational hypertension. Methods: IL-10 and TNF-αwere determined with ABC-ELISA in serum samples from 22 women with gestational hypertension, 24 women with preeclampsia, 18 women with eclampsia and 25 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly. Results: There were no significant differences in serum levels of IL-10 and TNF-α(P> 0. 05 for all) among normal pregnancy and gestational hypertension . There were significant differences in serum levels of IL-10 and TNF-α( p < 0.001 for all) among preeclampsia and eclampsia. The ratio of serum TNF-α/ IL-10 was no significantly higher among normal pregnancy and gestational hypertension (P>0.05), and the ratio of TNF-α/IL-10 significantly higher in patients with preeclampsia and eclampsia than that in either controls or gestational hypertension (P<0.001) .Conclusion: Gestational hypertension patients Th1-type cytokines TNF-αexpression increased, while Th2 cytokine IL-10 expression decline, Th1/Th2 ratio was significantly higher. Th1 / Th2 cytokines to the balance of Th1 migration, that is, enhance the functions of Th1 cells, decrease the functions of Th2 cells. Alterations of serum cytokine balance with predominance of Th1 immunity were observed in hypertensive disorder complicating pregnancy. These associations may offer insight into the pathogenesis of hypertensive disorder complicating pregnancy.
引文
[1]乐杰主编妇产科学.第7版北京.人民卫生出版社.2008,92-94
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[3]YONEYAMA Y,SUZUKI S,YONEYAMA K,et al.Relation between adenosine and T-helper 1/T-helper 2 imbalance in wonmen with preeclampsia.[J].Obsetet Gynecol.2002,99(4):641-646
[4]Heikkinen J,Mottonen M,Alanen A,et al.Phenotypic characterization of regulatory T cells in the human decidua.Clin Exp Immunol.2004,136(2):373-378
[5]Chaouat G.Innately moving away from the Th1/Th2 paradigm in pregnancy.[J].Clin Exp Immunol.2003,131(2):393-395
[6]Chaouat G,Zourbas S,Ostojie S,et al.A brief review of recent data on some cytokine expressions at the materno-foetal interface which mignt challenge the classical Th1/Th2 dichotom.[J].J Reprod Immunol.2002,53(1-2):241-256
[7]Aluvihare VR,Kallikourdis M,Betz AG.,et al.Tolerance,suppression and the fetal allograft.J Mol Med.2005,83(2):88-96
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[20]Chaouat G, Ledee B N,Zourbas S,et al.Implantation:can immunological parameters of implantation failure be of interest for preeclampsia. [J]. J Reprod Immunol.2003,59(1):205-217
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[24]Wilcaynski JR,Tchorzewski H,Banasik M,et al.Lymphocyte subset distribution and cytokine secretion in third trimester deciduas in normal pregnancy and preeclampsia.Eur J Obstet Gynecol Reprod Biol.2003,109(1):8-15
[25]Kuwajima T, Suzuki S, Yoneyama Y, et al.Relation between plasma endothelinllevels and T helperl:T help2cell immunity in women with preeclampsia. [J]. Gynecol Obstet Invest.2001,52(1):260-263
[26]SAITO S, SAKAI M.Th1/Th2 balance in preeclampsia.[J].J Reprod Immunol. 2003,59(2):161-173
[27]SAKAI M,OGAWA K,SHIOZAKI A,et al.Serum granulysin is a marker for Th1 type immunity in preeclampsia.[J].Clin Exp Immunol.2004,136(1):114-119
[28]Willzynski JR,Tchorzew ski H,Glowacka E,et al..Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre- clampsia.[J].Mediators Inflamm. 2002,11(2): 105-111
[29]Solomon CG,Seely EW.Preeclampsia-searching for the cause.N Engl Med.2004, 350(7):641-642
[30]Pang ZJ,Xing FQ.Comparative profiling of metabolism-related gene expression in pre-eclamptic and normal pregnancies.[J].Arch Gynecol Obstet.2004,269(2):91-95
[31]Rein D T,Schondorf T,Gohring U J,et al. Cytokine experession in peripheral blood lymphocytes indicates a switch to T helper cells in patients with preeclampsia. [J].J Reprod Immunol.2002,54(2):133-142
[32]Shunji Suzuki,Nozomi Ouchi.T Helper l/T Helper 2 Cell Immunity in Preeclamptic Pregnancy.J Nippon Med Sch Vol.2007,74(6):434-436
[33]WEI Jun,LIU kui-ran,SUI Li-hong,et al.Secretion of Thl and Th2 cytokines by peripheral blood mononuclear cells in preeclampsia. J China Journal of Moder Medicine.2005,15(16):2414-2416
[34]Ohkuchi A,Minakami H,Aoya T,et al. Expansion of the fraction of Thlcells in women with preeclampsia:Inverse correlation between the percentage of Thlcells and the plasma level of PAI-2 .[J].AJRI.2001,46(2):252-259
[35]Mello G,Parrelli E,Gensini F,el al.Maternal-fetal flow,negative events and preeclampsia Role of Th1/Th2 polymorphisa.[J].Hypertension.2003,41(4):932-937
[36]Serin YS,Ozcelik B,Bapbuo M,et al.Predictive value of tumor necrosis factor alpha(TNF-alpha)in preeclampsia.[J].Eur J Obstet Gynecol Reprod Biol.2002,100(2):143-145
[37]Dietl J.The pathogenesis of pre-eclampsia:new aspects.J Perinal Med.2000,28(1):464-471
[38]Beckmann I,Efraim SB,Vervoort M,et aI.Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and non pregnant women.[J].Hypertens Pregnancy.2004,23(2):319-329
[39]Hecskanon J,Romppanen EL,Hiltunen M,et al.polymorphism in the tumor necrosis factor-alpha gene in women with preeclampsia.[J].J Assist Reprod Genet.2002,19(5):220-223
[40]Knakstedt M,Ding JW,Arck PC,et al.Activation of the novel prothrom binase fg~(12),as a basis for the pregnany complications spontaneous abortion and preeclampsia.[J].Am J Reprod Immumol.2001,46(3):196-210
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[42]Reister F,Frank HG,Kingdom JC,et al.Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women.[J].Lab Invest.2001,81(8):1143-1152
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[2]Madazli R,Aydin S,Uludag S,et al.Maternal plasma levels of cytokines in normal and preeclamptic pregnancies and their relationship with diastotic blood pressure and fibronectin levels.[J].Acta Obstet Gyneeol Stand.2003,82(9):797-802
[3]YONEYAMA Y,SUZUKI S,YONEYAMA K,et al.Relation between adenosine and T-helper 1/T-helper 2 imbalance in wonmen with preeclampsia.[J].Obsetet Gynecol.2002,99(4):641-646
[4]Heikkinen J,Mottonen M,Alanen A,et al.Phenotypic characterization of regulatory T cells in the human decidua.Clin Exp Immunol.2004,136(2):373-378
[5]Chaouat G.Innately moving away from the Th1/Th2 paradigm in pregnancy.[J].Clin Exp Immunol.2003,131(2):393-395
[6]Chaouat G,Zourbas S,Ostojie S,et al.A brief review of recent data on some cytokine expressions at the materno-foetal interface which mignt challenge the classical Th1/Th2 dichotom.[J].J Reprod Immunol.2002,53(1-2):241-256
[7]Aluvihare VR,Kallikourdis M,Betz AG.,et al.Tolerance,suppression and the fetal allograft.J Mol Med.2005,83(2):88-96
[8]陈勇华.Th1/Th2型细胞因子与妊娠高血压综合征.[J].国外医学妇产科分册.2002,21(6):328
[9]赵媛媛.Th1/Th2失衡与妊娠高血压综合征.[J].国外医学妇幼保健分册.2004,15(2):42-43
[10]Somerset DA,Zheng Y,Kilby MD,et al.Normal human pregnancy is associated with an elevation in the immune suppressive CD25+CD4+regulatoryT-cell subset.[J].Immunology.2004,112(1):38-43
[11]Polanczyk MJ,Carson BD,Surbramanian S,et al.Cutting edge:estrogendrives expansion of the CD4+ CD25+ regulatory T cell compartment.J Immunol.2004,173(4):2227-2230
[12]Raghupathy R,Makhseed M,Azizich F,et al.cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion.J Hum Rrprod.2000,15(3):713-71 8
[13]Dimitrakova-Dzhambazova E,Milchev N,Pavlov P,et al.Lymphocyte populations and subpopulations in peripheral blood of pregnant women with preeclampsia.[J]. Akush Ginekol(Sofiia).2005,44(1):40-44
[14]Alexander BT,Cockrell K,Massey M,et al.Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression.[J].A M J Hypertens.2002,15(2):170-175
[15]Chaouat G,Ledee-Bataille N,Dubanchet S,et al.TH1/TH2 paradigm in pregnancy: paradigm lost? Cytokines in pregnancy/early abortion: reexamining the TH1/TH2 paradigm.[J].Int Arch Allergy Immunol.2004,134(2):93-119
[16]Clark DA,Blois S,Kandil J,et al.Reduced uterine indoleamine 2,3-dioxygenase versus increased Th1/Th2 cytokine ratios as a basis for occult and clinical ptegnancy failure in mice and humans.Am J Reprod Immunol.2005,54(4):203-216
[17]KocyigitY,AtamerY,AtamerA,et al.Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic an normotensive pregnant women.Gynecol Edocrinol. 2004, 19(5):267
[18]Daher S,Sass N,Mattar R,et al.Cytokine genotyping in preeclampsia.Am J Reprod Immunol.2006,55(2): 130-135
[19]Dorota Darmochwal-Kolarz,Jacek Rolinski,Bozena Leszczynska-Gorzelak,et al. The Expressions of Intracellular Cytokines in the Lymphocytes of Preeclamptic Patients.American Journal of Reproductive Immunology. 2002,48 (6):381 386
[20]Chaouat G, Ledee B N,Zourbas S,et al.Implantation:can immunological parameters of implantation failure be of interest for preeclampsia. [J]. J Reprod Immunol.2003,59(1):205-217
[21]Darmochwal-Kolarz D,Rolinski J,Leszczynska-GoarzeIak B,et al.The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients. Am J Reprod Immunol.2002,48(6):381-386
[22]Chappell s,Morgan L.Searching for genetic clues to the cause of pre-eclam psia.[J].Clin Sei(Lond).2006,110(4):443-458
[23]Toyohiko Kuwajima, Shunji Suzuki,Yoshio Yoneyama,et al.Relation between Plasma Endothelin 1 Levels and T Helper 1 :T Helper 2 Cell Immunity in Women with Preeclampsia. Am J Reprod Immunol.2001,52(4):260-263
[24]Wilcaynski JR,Tchorzewski H,Banasik M,et al.Lymphocyte subset distribution and cytokine secretion in third trimester deciduas in normal pregnancy and preeclampsia.Eur J Obstet Gynecol Reprod Biol.2003,109(1):8-15
[25]Kuwajima T, Suzuki S, Yoneyama Y, et al.Relation between plasma endothelinllevels and T helperl:T help2cell immunity in women with preeclampsia. [J]. Gynecol Obstet Invest.2001,52(1):260-263
[26]SAITO S, SAKAI M.Th1/Th2 balance in preeclampsia.[J].J Reprod Immunol. 2003,59(2):161-173
[27]SAKAI M,OGAWA K,SHIOZAKI A,et al.Serum granulysin is a marker for Th1 type immunity in preeclampsia.[J].Clin Exp Immunol.2004,136(1):114-119
[28]Willzynski JR,Tchorzew ski H,Glowacka E,et al..Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre- clampsia.[J].Mediators Inflamm. 2002,11(2): 105-111
[29]Solomon CG,Seely EW.Preeclampsia-searching for the cause.N Engl Med.2004, 350(7):641-642
[30]Pang ZJ,Xing FQ.Comparative profiling of metabolism-related gene expression in pre-eclamptic and normal pregnancies.[J].Arch Gynecol Obstet.2004,269(2):91-95
[31]Rein D T,Schondorf T,Gohring U J,et al. Cytokine experession in peripheral blood lymphocytes indicates a switch to T helper cells in patients with preeclampsia. [J].J Reprod Immunol.2002,54(2):133-142
[32]Shunji Suzuki,Nozomi Ouchi.T Helper l/T Helper 2 Cell Immunity in Preeclamptic Pregnancy.J Nippon Med Sch Vol.2007,74(6):434-436
[33]WEI Jun,LIU kui-ran,SUI Li-hong,et al.Secretion of Thl and Th2 cytokines by peripheral blood mononuclear cells in preeclampsia. J China Journal of Moder Medicine.2005,15(16):2414-2416
[34]Ohkuchi A,Minakami H,Aoya T,et al. Expansion of the fraction of Thlcells in women with preeclampsia:Inverse correlation between the percentage of Thlcells and the plasma level of PAI-2 .[J].AJRI.2001,46(2):252-259
[35]Mello G,Parrelli E,Gensini F,el al.Maternal-fetal flow,negative events and preeclampsia Role of Th1/Th2 polymorphisa.[J].Hypertension.2003,41(4):932-937
[36]Serin YS,Ozcelik B,Bapbuo M,et al.Predictive value of tumor necrosis factor alpha(TNF-alpha)in preeclampsia.[J].Eur J Obstet Gynecol Reprod Biol.2002,100(2):143-145
[37]Dietl J.The pathogenesis of pre-eclampsia:new aspects.J Perinal Med.2000,28(1):464-471
[38]Beckmann I,Efraim SB,Vervoort M,et aI.Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and non pregnant women.[J].Hypertens Pregnancy.2004,23(2):319-329
[39]Hecskanon J,Romppanen EL,Hiltunen M,et al.polymorphism in the tumor necrosis factor-alpha gene in women with preeclampsia.[J].J Assist Reprod Genet.2002,19(5):220-223
[40]Knakstedt M,Ding JW,Arck PC,et al.Activation of the novel prothrom binase fg~(12),as a basis for the pregnany complications spontaneous abortion and preeclampsia.[J].Am J Reprod Immumol.2001,46(3):196-210
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