Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension
Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension
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DOI：
10.1152/ajpregu.00590.2007
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发表时间：
2008-02-01
影响因子：
2.8
通讯作者：
Iversen, Bjarne M.
中科院分区：
文献类型：
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作者：
Bivol, Liliana M.;Berge, Rolf K.;Iversen, Bjarne M.
ANG II通过核因子-κ B（NF-κ B）介导的细胞因子和活性氧（ROS）诱导促进炎症。本研究的目的是检查十四烷基硫代乙酸（TTA），一种修饰的脂肪酸，对NF-κ B，促炎标志物，ROS和一氧化氮（NO）的生产在两肾一夹（2K 1C）高血压的影响。2K 1C TTA治疗组的血压（128 ± 3 mmHg）低于2K 1C未治疗组（178 ± 5 mmHg，P < 0.001）。与对照组（分别为0.25 +/- 0.03和0.12 +/- 0.02，P +/-0.001）相比，在切除肾脏中NF-κ B的p50和p65亚基（分别为0.44 +/- 0.01和0.22 +/-0.01）更高。在2K 1C TTA给药组中，这些值与对照水平相似。在未夹闭的肾脏中也观察到了相同的反应模式。2K 1C高血压患者血浆细胞因子水平高于对照组：TNF-α为13.5 +/- 2 pg/ml（P < 0.03），IL-1 β为58.8 ± 10 pg/ml IL- 6为210 +/- 33 pg/ml（P < 0.001），单核细胞趋化蛋白-1为429 +/- 21 pg/ml（P = 0.04）。在2K 1C TTA给药组中，这些值与对照组相似，并且在切除的肾脏中观察到相同的模式。结扎增加了尿中8-iso-PGF-2 α（P < 0.01），减少了NO的产生（P < 0.01 vs.对照）。TTA治疗使这些值正常化。切肾组和非切肾组NO生成量也较低（P < 0.001）。TTA处理后，这些值与对照组相似。结果表明，TTA通过抑制p50/p65 NF-κ B亚基活化，减少细胞因子和ROS的产生，并增加NO的产生，在2K 1C中具有有效的抗炎作用。
ANG II promotes inflammation through nuclear factor-kappa B (NF-kappa B)-mediated induction of cytokines and reactive oxygen species (ROS). The aim of the present study was to examine the effect of tetradecylthioacetic acid (TTA), a modified fatty acid, on NF-kappa B, proinflammatory markers, ROS, and nitric oxide (NO) production in two-kidney, one-clip (2K1C) hypertension. The 2K1C TTA-treated group had lower blood pressure (128 +/- 3 mmHg) compared with 2K1C nontreated (178 +/- 5 mmHg, P < 0.001). The p50 and p65 subunits of NF-kappa B were higher in the clipped kidney (0.44 +/- 0.01 and 0.22 +/- 0.01, respectively) compared with controls (0.25 +/- 0.03 and 0.12 +/- 0.02, respectively, P +/- 0.001). In the 2K1C TTA-treated group, these values were similar to control levels. The same pattern of response was seen in the nonclipped kidney. In 2K1C hypertension, cytokines plasma were higher than in control: TNF-alpha was 13.5 +/- 2 pg/ml (P < 0.03), IL-1 beta was 58.8 +/- 10 pg/ml (P = 0.003), IL- 6 was 210 +/- 33 pg/ml (P < 0.001), and monocyte chemoattractant protein-1 was 429 +/- 21 pg/ml (P = 0.04). In the 2K1C TTA-treated group, these values were similar to controls, and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF-2 alpha (P < 0.01) and decreased NO production (P < 0.01 vs. control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and nonclipped kidney (P < 0.001). After TTA treatment, these values were similar to controls. The results indicate that TTA has a potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-kappa B subunit activation, reduction of cytokines production and ROS, and enhanced NO production.