Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
Department of Endocrinology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545005, China.
Eur J Pharmacol. 2014 Oct 5;740:9-14. doi: 10.1016/j.ejphar.2014.06.055. Epub 2014 Jul 5.
Atorvastatin (AT) has been alternatively used for managing diabetic complications in clinic. However, AT-related therapeutic potentiality remains relatively unexplored, especially in diabetic nephropathy. This study aimed to investigate the underlying potentiality that AT exerted on anti-diabetic nephropathy role against streptozotocin (STZ)-induced kidney injury in rats. STZ-diabetic rats were intragastrically administered with AT (10, 20 mg/kg/d) for consecutive 8 weeks. The effects of AT on body weight, levels of blood glucose, lipometabolism, redox state, cellular metabolism, regulator factor and kidney morphological changes were monitored by routine measurement, biochemistry assay, PT-PCR analysis, ultrastructural and pathological observations, respectively. Compared with the diabetic nephropathy rats, AT elevated the body weight of diabetic nephropathy rats (P<0.01), effectively reduced the blood glucose level (P<0.01), increased the levels of insulin and high-density lipoprotein cholesterol (HDL-C) in plasma (P<0.01), and decreased the 24 h urine protein content and serum concentrations of low-density lipoprotein cholesterol (LDL-C) (P<0.01). Meanwhile, increase in kidney tissue, the intrarenal activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced, while the malonaldehyde (MDA) content was reduced (P<0.01). In addition, the expression of transforming growth factor beta 1 (TGF-β1) mRNA in kidney tissue was notably down-regulated (P<0.01). Furthermore, AT contributed to alleviating STZ-induced nephritic damages in rats. These results demonstrate that atorvastatin exerts the effective protective role against kidney injuries of STZ-induced diabetic nephropathy rat, which the underlying mechanisms are associated with ameliorating glyco, lipometabolism, enhancing antioxidant ability, and mitigating renal damage.
阿托伐他汀（AT）已在临床上被用于治疗糖尿病并发症。然而，AT 的相关治疗潜力仍未得到充分探索，尤其是在糖尿病肾病方面。本研究旨在探讨 AT 在链脲佐菌素（STZ）诱导的大鼠肾脏损伤中的抗糖尿病肾病作用的潜在机制。STZ 诱导的糖尿病大鼠连续 8 周每天经胃内给予 AT（10、20mg/kg/d）。通过常规测量、生化测定、PT-PCR 分析、超微结构和病理观察，分别监测 AT 对体重、血糖水平、脂代谢、氧化还原状态、细胞代谢、调节因子和肾脏形态变化的影响。与糖尿病肾病大鼠相比，AT 增加了糖尿病肾病大鼠的体重（P<0.01），有效降低了血糖水平（P<0.01），增加了血浆中胰岛素和高密度脂蛋白胆固醇（HDL-C）的水平（P<0.01），并降低了 24 小时尿蛋白含量和血清中低密度脂蛋白胆固醇（LDL-C）的浓度（P<0.01）。同时，肾脏组织中，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性增加，而丙二醛（MDA）的含量降低（P<0.01）。此外，肾脏组织中转化生长因子-β1（TGF-β1）mRNA 的表达显著下调（P<0.01）。此外，AT 有助于缓解 STZ 诱导的大鼠肾炎损伤。这些结果表明，阿托伐他汀对 STZ 诱导的糖尿病肾病大鼠的肾脏损伤具有有效的保护作用，其作用机制与改善糖、脂代谢、增强抗氧化能力和减轻肾脏损伤有关。
