Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Japan.
Am J Nephrol. 2011;34(3):281-90. doi: 10.1159/000330853. Epub 2011 Aug 9.
Diabetic bone disease is a major complication in diabetes mellitus and is characterized by low-turnover bone formation. Recent studies have demonstrated that oxidative stress could be associated with diabetic bone disease and that β-adrenergic antagonists could increase bone formation. Our study investigated the effect of carvedilol (β-blocker), possessing an antioxidant effect, on diabetic bone disease.
We used the non-obese, type 2 diabetes model Spontaneously Diabetic Torii (SDT) rats in this study. Sprague-Dawley rats were used as controls (control, n = 6). SDT rats were divided into four groups: diabetic (DM, n = 8), DM+insulin (DM+I, n = 7), DM+carvedilol (DM+C, n = 8), and DM+N-acetylcysteine (DM+N, n = 10) at 20 weeks. The rats were sacrificed at 30 weeks, after which blood and urine samples, bone mineral density, histomorphometry, and oxidative stress were evaluated.
The number of 8-hydroxydeoxyguanosine-positive cells in bone tissue was significantly lower in the DM+C and DM+N groups than in the DM group. Mineral apposition rate and bone formation rate per bone surface in the DM+C and DM+N groups were significantly higher than those in the DM group, and these parameters were better in the DM+C group than in the DM+N group.
Our data suggest that carvedilol has stronger effects on diabetic low-turnover bone disease beyond that which can be attributed to its antioxidative stress mechanism.
糖尿病性骨病是糖尿病的一种主要并发症,其特征为低转换型骨形成。最近的研究表明,氧化应激可能与糖尿病性骨病有关,β-肾上腺素能拮抗剂可以增加骨形成。我们的研究调查了具有抗氧化作用的卡维地洛(β受体阻滞剂)对糖尿病性骨病的影响。
我们在这项研究中使用了非肥胖 2 型糖尿病模型 Spontaneously Diabetic Torii(SDT)大鼠。将 Sprague-Dawley 大鼠作为对照(对照组,n = 6)。SDT 大鼠分为四组:糖尿病组(DM,n = 8)、DM+胰岛素组(DM+I,n = 7)、DM+卡维地洛组(DM+C,n = 8)和 DM+N-乙酰半胱氨酸组(DM+N,n = 10),在 20 周时进行分组。30 周时处死大鼠,评估血样、尿样、骨密度、组织形态计量学和氧化应激。
DM+C 和 DM+N 组骨组织中 8-羟基脱氧鸟苷阳性细胞的数量明显低于 DM 组。DM+C 和 DM+N 组的矿化沉积率和骨形成率/骨表面均明显高于 DM 组,且 DM+C 组优于 DM+N 组。
我们的数据表明,卡维地洛对糖尿病低转换型骨病的作用强于其抗氧化应激机制的作用。