α-Klotho和过氧化氢酶在原发性高血压中的表达

G. Pathare, S. Raju, M. Mashru, V. Shah, K. Shalia
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引用次数: 1

摘要

α-Klotho是一种抗衰老基因,在细胞水平上被认为是一种新的氧化应激抑制剂。α-Klotho通过抑制IGF-1/InsulinFOXO (Forkhead box-O转录因子)依赖的抗氧化酶失活来抑制氧化应激。本研究旨在测定印度人群原发性高血压患者外周血单个核细胞(PBMCs) α-Klotho和过氧化氢酶基因表达和过氧化氢酶活性,并与正常血压健康对照。招募了48名高血压患者和48名年龄,bmi匹配的对照组。采用实时荧光定量PCR检测基因表达。采用酶联免疫吸附法检测外周血过氧化氢酶活性和血清可溶性α-Klotho水平。与对照组相比,患者α-Klotho和FOXO1基因表达明显降低(p<0.001和p=0.002)。过氧化氢酶在高血压患者中的表达也较低,但无统计学意义。而α-Klotho与过氧化氢酶ΔCt-based基因表达量在患者与对照组之间呈显著正相关(p<0.001) (p=0.008)。高血压患者FOXO1基因表达与α-Klotho (p=0.006)、过氧化氢酶(p=0.001)呈正相关。与对照组相比,患者过氧化氢酶活性显著降低(p<0.001),与可溶性α-Klotho水平呈正相关(rs=0.32, p=0.027),患者组过氧化氢酶活性也降低了30.2% (p<0.001)。目前的研究表明,抗衰老蛋白α-Klotho在高血压患者中低可溶性水平和基因表达。α-Klotho可能通过对FOXO1表达的影响来影响原发性高血压过氧化氢酶的表达。
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α-Klotho and catalase expression in essential hypertension
α-Klotho, an anti-aging gene, has emerged as novel inhibitor of oxidative stress at cellular level. α-Klotho inhibits oxidative stress by inhibiting IGF-1/InsulinFOXO (Forkhead box-O transcription factors) dependent deactivation of the antioxidative enzymes. The present study aimed at determining α-Klotho and Catalase gene expressions and Catalase activity in peripheral blood mononuclear cells (PBMCs) of essential hypertensive patients as compared to normotensive healthy controls in Indian population. Forty-eight hypertensives and 48 age, BMI-matched controls were recruited. Gene expression was evaluated by quantitative Real-Time PCR. Catalase enzyme activity in PBMCs and soluble α-Klotho levels in serum were detected using Enzyme-Linked Immunosorbent Assay. Gene expressions for α-Klotho and FOXO1 were significantly low (p<0.001 and p=0.002, respectively) in patients as compared to controls. Catalase expression was also low in hypertensive patients but did not reach statistical significance. However, there was strong positive correlation between ΔCt-based gene expression of α-Klotho and Catalase in patients (p<0.001) as well as controls (p=0.008). Positive correlation was also observed between gene expression of FOXO1 and that of α-Klotho (p=0.006) and Catalase (p=0.001) in hypertensives. Catalase activity in patients were significantly low (p<0.001) as compared to controls and positively correlated with soluble α-Klotho levels (rs=0.32, p=0.027), which were also 30.2% lower (p<0.001) in the patient group. Present study demonstrates low soluble levels and gene expression of anti-aging protein α-Klotho in hypertensive patients. α-Klotho may influence Catalase expression in essential hypertension through its effect on FOXO1 expression.
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