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The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients

机译:替米沙坦对高血压患者激活的T淋巴细胞信号通路的核因子的影响

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Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China. T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively. There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls. Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.
机译:先前的研究提供了活化的T淋巴细胞(NFAT)信号通路的核因子与高血压的发展之间的联系。我们的初步研究表明,替米沙坦可以阻断Kv1.3钾通道并有效抑制钾电流密度,以及Kv1.3 mRNA和蛋白质表达水平。本文旨在研究在中国新疆哈萨克族原发性高血压(EH)患者中,替米沙坦对外周血T淋巴细胞活化和增殖后NFAT信号通路是否具有抑制作用。使用免疫磁性细胞分选方法(MACS)分离T淋巴细胞。通过定量聚合酶链反应(qRT-PCR)测量NFATc1,IL-6和TNF-α的mRNA表达,并通过蛋白质印迹法评估相对蛋白水平。来自新疆的50名哈萨克族高血压患者的T细胞样本被随机分为对照组,替米沙坦,环孢菌素A(CsA),VIVIT和4-氨基吡啶(4-AP)组。首先在体外激活并增殖外周血T淋巴细胞,然后在不同的处理条件下孵育48小时,然后分别通过Western blot和qRT-PCR分析确定NFATc1,IL-6和TNF-α的蛋白质和mRNA表达。在分配给五组样本的患者中,心血管危险因素无显着差异(p> 0.05)。与对照组相比,所有治疗组(替米沙坦,CsA,VIVIT和4-AP)的T淋巴细胞中NFATc1,IL-6和TNF-αmRNA和蛋白质的表达均显着降低。替米沙坦的抗高血压功能和对T淋巴细胞NFAT信号通路的抑制作用不太可能影响高血压患者的正常免疫功能。替米沙坦可通过抑制高血压患者T淋巴细胞中的NFAT信号传导途径发挥抗炎作用。

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