Klotho gene delivery suppresses oxidative stress in vivo
Klotho gene delivery suppresses oxidative stress in vivo
复制标题
DOI：
10.1111/j.1447-0594.2007.00406.x
复制
发表时间：
2007-09-01
影响因子：
3.3
通讯作者：
Ogihara, Toshio
中科院分区：
文献类型：
--
作者：
Ohta, Junsuke;Rakugi, Hiromi;Ogihara, Toshio
目的：klotho基因缺陷的小鼠表现出类似于人类早衰的综合征。最近的一份报告也表明，klotho转基因小鼠寿命长，这表明klotho是一种抗衰老基因。此前，klotho已被报道可以改善内皮功能障碍，并对氧化应激具有预防作用。在本研究中，我们研究了Klotho基因传递对血压和氧化stress.Methods的影响：Klotho质粒注射到小鼠和自发性高血压大鼠的尾静脉超过5 s。结果：Klotho基因传递上调锰超氧化物歧化酶蛋白表达和总超氧化物歧化酶活性在小鼠主动脉与对照组相比。它上调小鼠血清中一氧化氮的产生，并下调脂质过氧化物的浓度。当klotho质粒给药到自发性高血压大鼠，在肾脏和肝脏中的超氧化物歧化酶活性显着增加，脂质过氧化物浓度显着降低，与对照组相比。Klotho基因在自发性高血压大鼠中的传递没有改变收缩压。结论：这些结果表明，Klotho基因输注到小鼠和大鼠的尾静脉中具有抑制氧化应激的作用。这些发现可能为Klotho基因在体内调节氧化应激的治疗潜力提供新的见解。
Objective: Mice deficient in the klotho gene exhibit a syndrome resembling premature human aging. A recent report also suggested that klotho transgenic mice exhibited a long lifespan, which shows that klotho is an antisenescence gene. Previously, klotho has been reported to improve endothelial dysfunction, and also to have a preventive effect against oxidative stress. In the present study, we investigated the effect of klotho gene delivery on blood pressure and oxidative stress in vivo.Methods: Klotho plasmid was injected into the tail vein of mice and spontaneous hypertensive rats over 5 s.Results: Klotho gene delivery upregulated manganese superoxide dismutase protein expression and total superoxide dismutase activity in the aorta of mice compared with the control. It upregulated nitric oxide production, and downregulated lipid peroxide concentration in the serum of mice. When klotho plasmid was administered to spontaneously hypertensive rats, superoxide dismutase activity in the kidney and liver was significantly increased, and lipid peroxide concentration in the kidney and liver was significantly decreased, compared with the control. Klotho gene delivery in spontaneously hypertensive rats did not alter systolic blood pressure.Conclusion: These results suggest that klotho gene infusion into the tail vein of mice and rats has a suppressive effect against oxidative stress. These findings may provide a new insight into the therapeutic potential of klotho gene delivery in vivo to regulate oxidative stress.