肾素-血管紧张素系统在慢性束缚应激诱导的小鼠白细胞介素表达中的作用
|
摘要
目的探讨肾素-血管紧张素系统(renin-angiotensin system,RAS)在慢性束缚应激诱导下对小鼠白细胞介素表达的作用。方法以慢性束缚应激法建立应激模型,对其中部分小鼠注射血管紧张素转化酶抑制剂(angiotensin-converting enzyme inhibitor,ACEI)以阻断RAS。本实验将50只雄性C57小鼠随机平均分为5组:对照组(Ctrl)、束缚一周组(R1w)、束缚一周+ACEI组(R1w+ACEI)、束缚二周组(R2w)、束缚二周+ACEI组(R2w+ACEI),其中R1w+ACEI和R2w+ACEI两组束缚前30 min腹腔注射卡托普利,最后采用酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)测定血清中IL-2、IL-4、IL-6、IL-12的浓度。结果与Ctrl组相比,R1w组IL-2、IL-4、IL-6、IL-12浓度明显升高(P<0.05),R2w组IL-2、IL-4、IL-6浓度明显升高(P<0.05);卡托普利处理一周及二周以后IL-12的浓度显著下降(P<0.05)。结论慢性束缚应激初期可引起免疫因子IL-2、IL-4、IL-6、IL-12水平增高,机体处于高免疫活性状态。RAS参与了慢性束缚应激诱导的IL-12的激活,与IL-2、IL-4、IL-6无关。
Objective To investigate the effect of renin-angiotensin system(RAS)on the expression of interleukin in mice induced by chronic restraint stress. Methods A stress model was established by chronic restraint stress method.Some mice were injected with angiotensin-converting enzyme inhibitor(ACEI) to block RAS. In this experiment, 50 male C57 mice were randomly divided into 5 groups: control group(Ctrl), restraint one-week group(R1 w), restraint one week+ACEI group(R1 w+ACEI), restraint two-week group(R2 w), and restraint two-week +ACEI group(R2 w+ACEI),in which R1 w+ACEI and R2 w+ACEI were intraperitoneally injected with captopril 30 min before the restraint. And finally serum concentration of IL-2, of IL-4, IL-6 and IL-12 was determined by enzyme-linked immunosorbent assay(ELISA). Results Compared with that of the Ctrl group, the concentration of IL-2, IL-4, IL-6 and IL-12 in the R1 w group was significantly increased(P<0.05), and the concentration of IL-2, IL-4 and IL-6 in the R2 w group was significantly increased(P<0.05). IL-12 concentrations were significantly decreased after one week and two weeks of captopril treatment(P<0.05). Conclusion The early stage of chronic restraint stress can cause the levels of immune factors IL-2,IL-4, IL-6 and IL-12 to increase, and the body is in a state of high immunological activity. RAS is involved in the activation of IL-12 induced by chronic restraint stress, independent of IL-2, IL-4, and IL-6.
Objective To investigate the effect of renin-angiotensin system(RAS)on the expression of interleukin in mice induced by chronic restraint stress. Methods A stress model was established by chronic restraint stress method.Some mice were injected with angiotensin-converting enzyme inhibitor(ACEI) to block RAS. In this experiment, 50 male C57 mice were randomly divided into 5 groups: control group(Ctrl), restraint one-week group(R1 w), restraint one week+ACEI group(R1 w+ACEI), restraint two-week group(R2 w), and restraint two-week +ACEI group(R2 w+ACEI),in which R1 w+ACEI and R2 w+ACEI were intraperitoneally injected with captopril 30 min before the restraint. And finally serum concentration of IL-2, of IL-4, IL-6 and IL-12 was determined by enzyme-linked immunosorbent assay(ELISA). Results Compared with that of the Ctrl group, the concentration of IL-2, IL-4, IL-6 and IL-12 in the R1 w group was significantly increased(P<0.05), and the concentration of IL-2, IL-4 and IL-6 in the R2 w group was significantly increased(P<0.05). IL-12 concentrations were significantly decreased after one week and two weeks of captopril treatment(P<0.05). Conclusion The early stage of chronic restraint stress can cause the levels of immune factors IL-2,IL-4, IL-6 and IL-12 to increase, and the body is in a state of high immunological activity. RAS is involved in the activation of IL-12 induced by chronic restraint stress, independent of IL-2, IL-4, and IL-6.
引文
[1]Dhabhar FS.Effects of stress on immune function:The good,the bad,and the beautiful[J].Immunologic Research,2014,58(2-3):193-210.
[2]杨钢,万瑜,万曙霞,等.肾素-血管紧张素系统---应激激素反应系统[J].湖北医药学院学报,1995,(3):155-157.
[3]Wang LH,Dong T,Liu BB,et al.Contribution of the renin-angiotensin system in chronic foot-shock induced hypertension in rats[J].Life Sciences,2015,121:135-144.
[4]Crowley SD,Rudemiller NP.Immunologic effects of the renin-angiotensin system[J].Journal of the American Society of Nephrology,2017,28(5):1350-1361.
[5]Hisada Y,Sugaya T,Yamanouchi M,et al.AngiotensinⅡplays a pathogenic role in immune-mediated renal injury in mice[J].Journal of Clinical Investigation,1999,103(5):627.
[6]Nataraj C,Oliverio MI,Mannon RB,et al.AngiotensinⅡregulates cellular immune responses through a calcineurin-dependent pathway[J].Journal of Clinical Investigation,1999,104(12):1693-1701.
[7]Yin D,Tuthill D,Mufson RA,et al.Chronic restraint stress promotes lymphocyte apoptosis by modulating Cd95expression[J].Journal of Experimental Medicine,2000,191(8):1423-1428.
[8]Buynitsky T,Mostofsky DI.Restraint stress in biobehavioral research:Recent developments[J].Neuroscience&Biobehavioral Reviews,2009,33(7):1089-1098.
[9]王艳,张蒙夏,谭思杰,等.慢性应激与抑郁症发病机理研究进展[J].中南医学科学杂志,2015,(6):703-707.
[10]彭云丽,王雯英,蒋春雷,等.应激诱发抑郁症的细胞因子机制研究进展[J].生理学报,2013,65(2):229-236.
[11]王曼,胡贤,金魁和.慢性应激对大鼠脑内白介素-18表达的影响[J].中华行为医学与脑科学杂志,2010,19(5):405-407.
[12]Boyman O,Kolios AG,Raeber ME.Modulation of T cell responses by IL-2 and IL-2 complexes[J].Clinical&Experimental Rheumatology,2015,33(4 Suppl 92):54.
[13]Melissa A.Brown,John Hural.Functions of IL-4 and control of its expression[J].Crit Rev Immunol,1997,17(1):1.
[14]Hunter CA,Jones SA.IL-6 as a keystone cytokine in health and disease[J].Nature Immunology,2015,16(5):448-457.
[15]Wang Y,Fan KT,Li JM,et al.The regulation and activity of interleukin-12.[J].Frontiers in Bioscience,2012,4(3):888-899.
[16]Wohleb ES,Mckim DB,Sheridan JF,et al.Monocyte trafficking to the brain with stress and inflammation:A novel axis of immune-to-brain communication that influences mood and behavior[J].Front Neurosci,2014,8:447.
[17]治丁铭,刘岩,赵鸿飞,等.针刺对大鼠心肌组织细胞因子的影响[J].中国老年学杂志,2016,36(1):19-21.
[18]郑惠萍,张双伟,陈洁,等.毛冬青对慢性心力衰竭大鼠模型炎症相关因子的影响[J].中药新药与临床药理,2014,25(2):183-185.
[19]李建,胡淞,张才全,等.慢性束缚应激对昆明小鼠脾淋巴细胞免疫功能及小鼠前胃癌移植瘤生长的影响[J].癌症,2008,27(5):471-475.
[20]于丽娜,徐延敏.血管紧张素Ⅱ及其受体拮抗剂在动脉粥样硬化中的研究进展[J].实用心脑肺血管病杂志,2010,18(1):88-91.
[21]Ravichandran K,Ozkok A,Wang Q,et al.Antisense-mediated angiotensinogen inhibition slows polycystic kidney disease in mice with a targeted mutation in Pkd2[J].Am J Physiol Renal Physiol,2015,8(4):F349-357.
[22]Colombo MP,Trinchieri G.Interleukin-12 in anti-tumor immunity and immunotherapy[J].Cytokine&Growth Factor Reviews,2002,13(2):155-168.
[23]Trembleau S,Penna G,Gregori S,et al.IL-12 administration accelerates autoimmune diabetes in both wildtype and IFN-gamma-deficient nonobese diabetic mice,revealing pathogenic and protective effects of IL-12-induced IFN-gamma[J].Journal of Immunology,2003,170(11):5491.
[24]Mcintyre KW,Shuster DJ,Gillooly KM,et al.Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice[J].European Journal of Immunology,2010,26(12):2933-2938.
[25]Yawalkar N,Tscharner GR,Hassan A.Increased expression of IL-12p70 and IL-23 by multiple dendrit ic cell and macrophage subsets in plaque psoriasis[J].Journal of Dermatological Science,2009,54(2):99-105.
[2]杨钢,万瑜,万曙霞,等.肾素-血管紧张素系统---应激激素反应系统[J].湖北医药学院学报,1995,(3):155-157.
[3]Wang LH,Dong T,Liu BB,et al.Contribution of the renin-angiotensin system in chronic foot-shock induced hypertension in rats[J].Life Sciences,2015,121:135-144.
[4]Crowley SD,Rudemiller NP.Immunologic effects of the renin-angiotensin system[J].Journal of the American Society of Nephrology,2017,28(5):1350-1361.
[5]Hisada Y,Sugaya T,Yamanouchi M,et al.AngiotensinⅡplays a pathogenic role in immune-mediated renal injury in mice[J].Journal of Clinical Investigation,1999,103(5):627.
[6]Nataraj C,Oliverio MI,Mannon RB,et al.AngiotensinⅡregulates cellular immune responses through a calcineurin-dependent pathway[J].Journal of Clinical Investigation,1999,104(12):1693-1701.
[7]Yin D,Tuthill D,Mufson RA,et al.Chronic restraint stress promotes lymphocyte apoptosis by modulating Cd95expression[J].Journal of Experimental Medicine,2000,191(8):1423-1428.
[8]Buynitsky T,Mostofsky DI.Restraint stress in biobehavioral research:Recent developments[J].Neuroscience&Biobehavioral Reviews,2009,33(7):1089-1098.
[9]王艳,张蒙夏,谭思杰,等.慢性应激与抑郁症发病机理研究进展[J].中南医学科学杂志,2015,(6):703-707.
[10]彭云丽,王雯英,蒋春雷,等.应激诱发抑郁症的细胞因子机制研究进展[J].生理学报,2013,65(2):229-236.
[11]王曼,胡贤,金魁和.慢性应激对大鼠脑内白介素-18表达的影响[J].中华行为医学与脑科学杂志,2010,19(5):405-407.
[12]Boyman O,Kolios AG,Raeber ME.Modulation of T cell responses by IL-2 and IL-2 complexes[J].Clinical&Experimental Rheumatology,2015,33(4 Suppl 92):54.
[13]Melissa A.Brown,John Hural.Functions of IL-4 and control of its expression[J].Crit Rev Immunol,1997,17(1):1.
[14]Hunter CA,Jones SA.IL-6 as a keystone cytokine in health and disease[J].Nature Immunology,2015,16(5):448-457.
[15]Wang Y,Fan KT,Li JM,et al.The regulation and activity of interleukin-12.[J].Frontiers in Bioscience,2012,4(3):888-899.
[16]Wohleb ES,Mckim DB,Sheridan JF,et al.Monocyte trafficking to the brain with stress and inflammation:A novel axis of immune-to-brain communication that influences mood and behavior[J].Front Neurosci,2014,8:447.
[17]治丁铭,刘岩,赵鸿飞,等.针刺对大鼠心肌组织细胞因子的影响[J].中国老年学杂志,2016,36(1):19-21.
[18]郑惠萍,张双伟,陈洁,等.毛冬青对慢性心力衰竭大鼠模型炎症相关因子的影响[J].中药新药与临床药理,2014,25(2):183-185.
[19]李建,胡淞,张才全,等.慢性束缚应激对昆明小鼠脾淋巴细胞免疫功能及小鼠前胃癌移植瘤生长的影响[J].癌症,2008,27(5):471-475.
[20]于丽娜,徐延敏.血管紧张素Ⅱ及其受体拮抗剂在动脉粥样硬化中的研究进展[J].实用心脑肺血管病杂志,2010,18(1):88-91.
[21]Ravichandran K,Ozkok A,Wang Q,et al.Antisense-mediated angiotensinogen inhibition slows polycystic kidney disease in mice with a targeted mutation in Pkd2[J].Am J Physiol Renal Physiol,2015,8(4):F349-357.
[22]Colombo MP,Trinchieri G.Interleukin-12 in anti-tumor immunity and immunotherapy[J].Cytokine&Growth Factor Reviews,2002,13(2):155-168.
[23]Trembleau S,Penna G,Gregori S,et al.IL-12 administration accelerates autoimmune diabetes in both wildtype and IFN-gamma-deficient nonobese diabetic mice,revealing pathogenic and protective effects of IL-12-induced IFN-gamma[J].Journal of Immunology,2003,170(11):5491.
[24]Mcintyre KW,Shuster DJ,Gillooly KM,et al.Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice[J].European Journal of Immunology,2010,26(12):2933-2938.
[25]Yawalkar N,Tscharner GR,Hassan A.Increased expression of IL-12p70 and IL-23 by multiple dendrit ic cell and macrophage subsets in plaque psoriasis[J].Journal of Dermatological Science,2009,54(2):99-105.