自然杀伤T细胞在血管紧张素Ⅱ诱导的高血压中的作用
|
摘要
目的:通过构建Ang Ⅱ诱导的小鼠高血压模型,研究自然杀伤T细胞(NKT)的作用。方法:在CD1d基因敲除小鼠及野生对照小鼠中,采用缓释泵持续灌注血管紧张素Ⅱ(Ang Ⅱ)490ng·kg~(-1)·min~(-1),14 d建立小鼠高血压模型,尾动脉无创性血压测量方法监测小鼠血压的变化;HE染色观察小鼠主动脉壁厚度的变化;Masson染色观察主动脉血管纤维化的程度;实时荧光定量PCR检测血管组织中IL-6及TNF-α的表达;流式分析检测血管壁巨噬细胞的浸润。结果:与对照组相比,Ang Ⅱ灌注14 d明显升高小鼠的收缩压、血管壁的厚度及纤维化程度、血管组织的炎症因子IL-1β及TNF-αmRNA的表达及血管组织中巨噬细胞的浸润;重要的是,CD1d基因的敲除进一步加重以上变化。结论:自然杀伤T细胞通过减轻巨噬细胞的浸润拮抗了血管紧张素Ⅱ灌注引起的血压升高。
Objective: To investigate the effect of natural killer T cells in the development of hypertension in mice induced by Ang Ⅱ infusion and the possible underlying molecular mechanisms. Methods: Ang Ⅱ was infused for 14 days to duplicate hypertensive model in CD1 d knockout mice. The mouse non-invasive tailcuff system was used to measure the changes of blood pressure; H&E staining was used to measure vascular wall thickness,Masson staining was used to detect collagen deposition,quantative PCR was used to detect the mRNA levels of IL-1β,IL-6 and TNF-α; Flow cytometry was used to detect the infiltration of macrophage in vascular wall. Results: Compared with saline group,Ang Ⅱ infusion significantly increased blood pressure,vascular wall thickness,collagen deposition,the mRNA levels of IL-1β,IL-6,TNF-α and macrophage infiltration; Importantly,CD1 d gene knockout aggravates the above changes. Conclusion: Natural killer T cells can alleviate the development of hypertension by reducing macrophage infiltration.
Objective: To investigate the effect of natural killer T cells in the development of hypertension in mice induced by Ang Ⅱ infusion and the possible underlying molecular mechanisms. Methods: Ang Ⅱ was infused for 14 days to duplicate hypertensive model in CD1 d knockout mice. The mouse non-invasive tailcuff system was used to measure the changes of blood pressure; H&E staining was used to measure vascular wall thickness,Masson staining was used to detect collagen deposition,quantative PCR was used to detect the mRNA levels of IL-1β,IL-6 and TNF-α; Flow cytometry was used to detect the infiltration of macrophage in vascular wall. Results: Compared with saline group,Ang Ⅱ infusion significantly increased blood pressure,vascular wall thickness,collagen deposition,the mRNA levels of IL-1β,IL-6,TNF-α and macrophage infiltration; Importantly,CD1 d gene knockout aggravates the above changes. Conclusion: Natural killer T cells can alleviate the development of hypertension by reducing macrophage infiltration.
引文
[1]Ishimitsu T.point at issue in the japanese society of hypertension’s guielines for the management of hypertension(jsh2009)[J].Nihon Jinzo Gakkai shi,2009,51(4):456-460.
[2]冯仕勇,赵迎新,许勇.H型高血压患者动态血压的特点.心肺血管病杂志,2014,33:224-231.
[3]Harrison DG,Vinh A,Lob H,et al.Role of the adaptive immune system in hypertension[J].Curr opin Pharamacol,2010,10(2):203-207.
[4]Harrison DG,Guzik TJ,Lob HE,et al.Inflammation,immunity,and hypertension[J].Hypertension,2011,57(2):132-140.
[5]马东亮,刘石健骢,蔡国华,等.CD45+CD25+Foxp3+调节性T细胞与心血管疾病研究新进展,心肺血管病杂志,2014,33:308-311.
[6]Andoh Y,Ogura H,Satoh M,et al.Natural killer t cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein e-deficient mice[J].Immunobiol,2013,218(4):561-569.
[7]Mc Kee SJ,Mattarollo SR,Leggatt GR.Immunosuppressive roles of natural killer t(nkt)cells in the skin[J].J leukoc biol,2014,96(1):49-54.
[8]Singh AK,Gaur P,Shukla NK,et al.Differential dendritic cellmediated activation and functions of invariant nkt-cell subsets in oral cancer[J].Oral Dis,2015,21(1):e105-113.
[9]Yang M,Deng C,Wu D,et al.The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension[J].J Thromb Thrombolysis,2016,42(1):38-45.
[10]Justin Rucker A,Crowley SD.The role of macrophages in hypertension and its complications[J].Pflugers Arch,2017,469(3-4):419-430.
[11]Wenzel P,Knorr M,Kossmann S,et al.Lysozyme m-positive monocytes mediate angiotensin ii-induced arterial hypertension and vascular dysfunction[J].Circulation,2011,124(12):1370-1381.
[2]冯仕勇,赵迎新,许勇.H型高血压患者动态血压的特点.心肺血管病杂志,2014,33:224-231.
[3]Harrison DG,Vinh A,Lob H,et al.Role of the adaptive immune system in hypertension[J].Curr opin Pharamacol,2010,10(2):203-207.
[4]Harrison DG,Guzik TJ,Lob HE,et al.Inflammation,immunity,and hypertension[J].Hypertension,2011,57(2):132-140.
[5]马东亮,刘石健骢,蔡国华,等.CD45+CD25+Foxp3+调节性T细胞与心血管疾病研究新进展,心肺血管病杂志,2014,33:308-311.
[6]Andoh Y,Ogura H,Satoh M,et al.Natural killer t cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein e-deficient mice[J].Immunobiol,2013,218(4):561-569.
[7]Mc Kee SJ,Mattarollo SR,Leggatt GR.Immunosuppressive roles of natural killer t(nkt)cells in the skin[J].J leukoc biol,2014,96(1):49-54.
[8]Singh AK,Gaur P,Shukla NK,et al.Differential dendritic cellmediated activation and functions of invariant nkt-cell subsets in oral cancer[J].Oral Dis,2015,21(1):e105-113.
[9]Yang M,Deng C,Wu D,et al.The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension[J].J Thromb Thrombolysis,2016,42(1):38-45.
[10]Justin Rucker A,Crowley SD.The role of macrophages in hypertension and its complications[J].Pflugers Arch,2017,469(3-4):419-430.
[11]Wenzel P,Knorr M,Kossmann S,et al.Lysozyme m-positive monocytes mediate angiotensin ii-induced arterial hypertension and vascular dysfunction[J].Circulation,2011,124(12):1370-1381.