Li Dao, Li Jin, Li Hui, Wu Qiong, Li Qi-Xiong
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China.
Department of Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China.
Iran J Basic Med Sci. 2016 Jul;19(7):749-54.
Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions.
Fifty male Sprague-Dawley rats weighing 250-300 g were randomly divided into five groups: administrations of olive oil (control, PO), RG (0.4 mg/kg, PO), CsA (30 mg/kg in olive oil, SC), RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil SC) every day for 15 days.
SC administration of CsA (30 mg/kg) to rats produced marked elevations in the levels of renal impairment parameters such as urinary protein, N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine (SCr), and blood urea nitrogen (BUN). It also caused histologic injury to the kidneys. Oral administration of RG (0.2 and 0.4 mg/kg) markedly decreased all the aforementioned changes. In addition, CsA caused increases in the levels of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione in kidney homogenate, which were reversed significantly by both doses of RG.
The findings of our study indicate that RG may play an important role in protecting the kidney from oxidative insult.
瑞格列奈（RG）是一种用于治疗非胰岛素依赖型糖尿病的降糖药物。它在伴有肾功能损害并发症的糖尿病患者中具有良好的安全性和疗效，即使对于肾功能损害程度更严重的个体也是一种合适的治疗选择。本研究的目的是研究RG对环孢素A（CsA）诱导的大鼠肾功能损害的保护作用，并评估RG发挥其保护作用的抗氧化机制。
50只体重250 - 300 g的雄性Sprague-Dawley大鼠随机分为五组：分别给予橄榄油（对照组，经口给药）、RG（0.4 mg/kg，经口给药）、CsA（30 mg/kg溶于橄榄油，皮下注射）、RG（0.2或0.4 mg/kg，经口给药）加CsA（30 mg/kg溶于橄榄油皮下注射），每天给药，持续15天。
给大鼠皮下注射CsA（30 mg/kg）导致肾功能损害参数水平显著升高，如尿蛋白、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、血清肌酐（SCr）和血尿素氮（BUN）。它还对肾脏造成了组织学损伤。口服RG（0.2和0.4 mg/kg）显著减轻了上述所有变化。此外，CsA导致肾匀浆中丙二醛（MDA）水平升高，超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽还原酶（GSR）、谷胱甘肽-S-转移酶（GST）和谷胱甘肽水平降低，而两种剂量的RG均能显著逆转这些变化。
我们的研究结果表明，RG可能在保护肾脏免受氧化损伤方面发挥重要作用。
