Reduction of circulating superoxide dismutase activity in type 2 diabetic patients with microalbuminuria and its modulation by telmisartan therapy
Reduction of circulating superoxide dismutase activity in type 2 diabetic patients with microalbuminuria and its modulation by telmisartan therapy
复制标题
DOI：
10.1038/hr.2011.127
复制
发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Yamada, Yuichiro
中科院分区：
文献类型：
--
作者：
Fujita, Hiroki;Sakamoto, Takuya;Yamada, Yuichiro
越来越多的证据表明，过量的超氧化物引起的氧化应激在糖尿病肾病（DN）的发病机制中起着重要作用。替米沙坦是目前可用的血管紧张素II 1型受体阻滞剂（ARB）之一，已显示可更有效地减少DN患者的蛋白尿（白蛋白尿），但替米沙坦的显著肾脏保护作用是否通过增强抗氧化防御能力和降低氧化应激介导尚未完全阐明。本研究首次揭示了负责清除超氧化物的超氧化物歧化酶（SOD）的血清活性在微量白蛋白尿的DN阶段降低，但在2型糖尿病患者的正常白蛋白尿中不降低。我们接下来检查了12例2型糖尿病伴微量白蛋白尿患者接受替米沙坦（40 mg/d）治疗8周后SOD和氧化应激的变化。有趣的是，替米沙坦治疗不仅降低了两种氧化应激标志物8-羟基-2 '-脱氧鸟苷（8-OHdG）和硝基酪氨酸（NT）的循环水平，还增强了血清SOD活性。值得注意的是，血清SOD活性的增加和白蛋白尿的减少之间观察到显着的相关性。我们通过在另外12例微量白蛋白尿的2型糖尿病患者中使用这些ARB进行8周间隔交叉治疗，进一步比较了替米沙坦与氯沙坦（ARB类的另一个成员）的抗氧化作用。与氯沙坦组相比，替米沙坦组患者血清SOD活性升高，循环中8-OHdG和NT水平降低。这些结果表明，替米沙坦通过增强伴有微量白蛋白尿的2型糖尿病患者的SOD活性，具有更有效的抗氧化作用。高血压研究（2011）34，1302-1308; doi：10.1038/hr.2011.127; 2011年8月4日在线发表
Growing evidence indicates that oxidative stress induced by excessive superoxide has a central role in the pathogenesis of diabetic nephropathy (DN). Telmisartan, one of the currently available angiotensin II type 1 receptor blockers (ARBs), has been shown to exert a more powerful proteinuria (albuminuria) reduction in patients with DN, but whether the prominent renoprotective effect of telmisartan is mediated through enhancing antioxidant defense capacity and reducing oxidative stress has not been fully elucidated. The present study first revealed that the serum activity of superoxide dismutase (SOD) responsible for superoxide removal is reduced in the DN stage of microalbuminuria, but not in normoalbuminuria in type 2 diabetic patients. We next examined the alteration of SOD and oxidative stress following an 8-week treatment with telmisartan (40 mg per day) in 12 type 2 diabetic patients with microalbuminuria. Interestingly, the telmisartan treatment not only reduced the circulating levels of two oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine (NT), but also enhanced serum SOD activity. Notably, a significant correlation was observed between the increase in serum SOD activity and the reduction in albuminuria. We further compared the anti-oxidative effect of telmisartan with that of losartan, another member of the ARB class, by implementing an 8-week interval crossover treatment with these ARBs in another 12 microalbuminuric type 2 diabetic patients. The patients showed higher serum SOD activity, and lower circulating levels of 8-OHdG and NT, during treatment with telmisartan than with losartan. These results suggest that telmisartan has a more potent antioxidative effect through its ability to enhance SOD activity in type 2 diabetic patients with microalbuminuria. Hypertension Research (2011) 34, 1302-1308; doi:10.1038/hr.2011.127; published online 4 August 2011