长期给予硝酸钠对肥胖 2 型糖尿病雄性大鼠糖尿病诱导性贫血和葡萄糖稳态的影响。
Effect of long-term sodium nitrate administration on diabetes-induced anemia and glucose homeostasis in obese type 2 diabetic male rats.
机构信息
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
Nitric Oxide. 2019 May 1;86:21-30. doi: 10.1016/j.niox.2019.02.003. Epub 2019 Feb 14.
PURPOSE
Anemia is common in patients with type 2 diabetes. This aims at determining long-term effects of nitrate administration on diabetes-induced anemia in obese type 2 diabetic rats.
METHODS
Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Type 2 diabetes was induced using high-fat diet followed by injection of streptozotocin (30 mg/kg). Sodium nitrate (100 mg/L in drinking water) was administered for six months. After overnight fasting, levels of glucose and erythropoietin (EPO) and complete blood cell count (CBC) were measured at month 0, month 3, and month 6. At month 6, serum iron, and testosterone as well as EPO protein levels and hypoxia-inducible factor-1 (HIF-1) mRNA levels in kidney and liver were measured.
RESULTS
Nitrate administration decreased serum glucose in diabetic rats by 10% and 15% at months 3 and 6, respectively. Nitrate restored decreased red blood cells count, hemoglobin concentration, and hematocrit to control levels in diabetic rats; in addition, nitrate restored decreased serum, kidney, and liver EPO levels to near normal values. Nitrate also increased HIF-1 mRNA levels in both kidney and liver of diabetic rats. Diabetic rats had lower serum testosterone (37%) and iron (20%) and nitrate restored these parameters to near normal values.
CONCLUSION
Long-term and low dose of nitrate had beneficial effects against anemia in obese type 2 diabetic rats; these effects were associated with increased EPO and HIF-1 levels in kidney and liver as well as increased circulating EPO, testosterone, and iron.
目的
贫血在 2 型糖尿病患者中很常见。本研究旨在确定硝酸盐给药对肥胖 2 型糖尿病大鼠糖尿病性贫血的长期影响。
方法
雄性 Wistar 大鼠分为 4 组：对照组、对照组+硝酸盐、糖尿病组和糖尿病+硝酸盐。通过高脂肪饮食和链脲佐菌素（30mg/kg）注射诱导 2 型糖尿病。给予亚硝酸钠（饮用水中 100mg/L）六个月。过夜禁食后，在第 0 个月、第 3 个月和第 6 个月测量血糖和促红细胞生成素（EPO）水平以及全血细胞计数（CBC）。第 6 个月时，测量血清铁、睾酮以及肾脏和肝脏中 EPO 蛋白水平和缺氧诱导因子-1（HIF-1）mRNA 水平。
结果
硝酸盐给药分别使糖尿病大鼠的血清葡萄糖在第 3 个月和第 6 个月降低了 10%和 15%。硝酸盐使糖尿病大鼠的红细胞计数、血红蛋白浓度和血细胞比容恢复至对照水平；此外，硝酸盐使降低的血清、肾脏和肝脏 EPO 水平恢复至接近正常水平。硝酸盐还增加了糖尿病大鼠肾脏和肝脏中的 HIF-1mRNA 水平。糖尿病大鼠的血清睾酮（37%）和铁（20%）较低，硝酸盐将这些参数恢复至接近正常水平。
结论
长期和低剂量的硝酸盐对肥胖 2 型糖尿病大鼠的贫血具有有益作用；这些作用与肾脏和肝脏中 EPO 和 HIF-1 水平的增加以及循环 EPO、睾酮和铁的增加有关。
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