Department of Pharmacology, St. Peter's Institute of Pharmaceutical Sciences, Hanmakonda, Warangal, Andhra Pradesh 506001, India.
Biol Trace Elem Res. 2011 Jan;139(1):55-71. doi: 10.1007/s12011-010-8635-z. Epub 2010 Feb 20.
To investigate whether sodium selenate treatment would impact on the onset of diabetic nephropathy, we examined blood glucose, serum biochemical components, and interrelationship between oxidative stress, TGF-β1, and apoptosis in streptozotocin (STZ) induced diabetic rats. Sixty male Wistar rats were divided into six groups. Group I (n = 10), normal control; Group II (n = 10), diabetic control; Group III (n = 10), sodium selenate (16 μmoles/kg) + diabetic; Group IV (n = 10), sodium selenate (32 μmoles/kg) + diabetic; Group V (n = 10), sodium selenate (16 μmoles/kg) control; and Group VI (n = 10), sodium selenate (32 μmoles/kg) control. Sodium selenate was administered via orogastric route for 10 weeks. In the diabetic group, diabetes was induced by single intraperitoneal injection of STZ (50 mg/kg). The levels of blood glucose were estimated and total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, creatinine, urea, and albumin were detected in serum. Antioxidant status was examined by measuring the superoxide dismutase (SOD), catalase, glutathione, and lipid peroxidation in kidney tissues. Histopathological studies were performed in the kidney tissue sections. The expression of TGF-β1 was estimated by the immunohistochemical analysis in kidneys. Apoptotic study in kidney was performed using the TdT-mediated dUTP nick end labeling technique. It was observed that blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin were significantly higher in diabetic control groups. Diabetic + sodium selenate (16 and 32 μmoles/kg) significantly reduced blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin levels. Selenium-treated groups significantly increased antioxidant enzyme activities (SOD, catalase, and glutathione) in kidneys of diabetic rats. All enzyme activities of selenium control groups did not differ compared with the normal control. Sodium selenate reduces significantly lipid peroxidation in diabetic rats. Cellular architecture of the diabetic rats was altered whereas sodium selenate administration rectifies the degenerative changes of the kidney. Profound immunopositivity of TGF-β1 was observed in the glomerular and tubulointerstitial cells of diabetic rat kidney. Immunopositivity of TGF-β1 was significantly reduced in both low and high dose of sodium-selenate-treated rats (P < 0.05, P < 0.01). High numbers of apoptotic cells were observed in diabetic rats whereas sodium selenate in both doses significantly reduces the incidence of apoptosis (P < 0.05, P < 0.01). We conclude herein that sodium selenate has the potential to play a significant role in limiting the renal impairment by altering the apoptosis and TGF-β1 in experimental diabetic rats.
为了研究亚硒酸钠治疗是否会影响糖尿病肾病的发病，我们检测了链脲佐菌素（STZ）诱导的糖尿病大鼠的血糖、血清生化成分以及氧化应激、TGF-β1 和细胞凋亡之间的相互关系。将 60 只雄性 Wistar 大鼠分为 6 组。第 I 组（n=10），正常对照组；第 II 组（n=10），糖尿病对照组；第 III 组（n=10），亚硒酸钠（16μmoles/kg）+糖尿病组；第 IV 组（n=10），亚硒酸钠（32μmoles/kg）+糖尿病组；第 V 组（n=10），亚硒酸钠（16μmoles/kg）对照组；第 VI 组（n=10），亚硒酸钠（32μmoles/kg）对照组。亚硒酸钠通过口服途径给药，持续 10 周。在糖尿病组中，通过单次腹腔注射 STZ（50mg/kg）诱导糖尿病。估计血糖水平，并检测血清总胆固醇、高密度脂蛋白（HDL）胆固醇、甘油三酯、肌酐、尿素和白蛋白。通过测量肾脏组织中的超氧化物歧化酶（SOD）、过氧化氢酶、谷胱甘肽和脂质过氧化物来检测抗氧化状态。在肾脏组织切片中进行组织病理学研究。通过免疫组化分析估计肾脏中 TGF-β1 的表达。使用末端转移酶介导的 dUTP 缺口末端标记技术（TUNEL）在肾脏中进行细胞凋亡研究。结果发现，糖尿病对照组的血糖、血清、总胆固醇、HDL 胆固醇、甘油三酯、肌酐、尿素和白蛋白水平显著升高。糖尿病+亚硒酸钠（16 和 32μmoles/kg）组显著降低了糖尿病大鼠的血糖、血清、总胆固醇、HDL 胆固醇、甘油三酯、肌酐、尿素和白蛋白水平。硒处理组显著增加了糖尿病大鼠肾脏中的抗氧化酶活性（SOD、过氧化氢酶和谷胱甘肽）。硒对照组的所有酶活性与正常对照组相比均无差异。亚硒酸钠可显著降低糖尿病大鼠的脂质过氧化。糖尿病大鼠的细胞结构发生改变，而亚硒酸钠的给药纠正了肾脏的退行性变化。在糖尿病大鼠的肾小球和肾小管间质细胞中观察到 TGF-β1 的强烈免疫阳性。两种剂量的亚硒酸钠治疗均显著降低 TGF-β1 的免疫阳性（P<0.05，P<0.01）。糖尿病大鼠中观察到大量凋亡细胞，而两种剂量的亚硒酸钠均可显著降低细胞凋亡的发生率（P<0.05，P<0.01）。我们的结论是，亚硒酸钠具有通过改变实验性糖尿病大鼠的细胞凋亡和 TGF-β1 来限制肾脏损害的潜力。
