Turk J Med Sci. 2018 Aug 16;48(4):880-885. doi: 10.3906/sag-1707-44.
BACKGROUND/AIM: Repaglinide (RG) is a prandial glucose regulator used for the treatment of type 2 diabetes. Our recent study showed that RG plays an important role in cyclosporine A (CsA)-induced nephrotoxicity through its antioxidant properties. However, it is not known whether or not RG has any protective effect on CsA-induced renal tubular toxicity by affecting apoptosis and expression of apoptosis-associated protein. The purpose of this study was to investigate the effects of RG on CsA-induced renal tubule apoptosis and Bax and Bcl-2 protein expression in rats.
Forty male Sprague Dawley rats weighing 250–300 g were randomly divided into four groups: administrations of olive oil (control, per os (PO)), CsA (30 mg/kg in olive oil, subcutaneous (SC)), and RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil, SC) every day for 15 days.
Our results showed that SC administration of CsA (30 mg/kg) to rats produced marked injury and apoptosis, elevation of Bax protein expression, and inhibition of Bcl-2 protein expression in the kidneys, which were reversed significantly by oral administration of RG (0.2 or 0.4 mg/kg).
The findings of our study indicate that RG may play an important role in protecting the kidneys through inhibiting apoptosis, Bax , and Bcl-2 protein expression.
背景/目的:瑞格列奈(RG)是一种用于治疗 2 型糖尿病的餐时血糖调节剂。我们最近的研究表明,RG 通过其抗氧化特性在环孢素 A(CsA)诱导的肾毒性中发挥重要作用。然而,尚不清楚 RG 是否通过影响细胞凋亡和凋亡相关蛋白的表达对 CsA 诱导的肾小管毒性具有保护作用。本研究的目的是探讨 RG 对 CsA 诱导的大鼠肾小管细胞凋亡和 Bax 和 Bcl-2 蛋白表达的影响。
40 只雄性 Sprague Dawley 大鼠,体重 250-300 g,随机分为四组:橄榄油(对照组,口服(PO))、CsA(橄榄油中的 30 mg/kg,皮下(SC))、RG(0.2 或 0.4 mg/kg,PO)加 CsA(橄榄油中的 30 mg/kg,SC),每天一次,共 15 天。
我们的结果表明,SC 给予大鼠 CsA(30 mg/kg)可导致肾脏明显损伤和凋亡,Bax 蛋白表达升高,Bcl-2 蛋白表达抑制,而 RG(0.2 或 0.4 mg/kg,PO)可显著逆转这些变化。
本研究结果表明,RG 通过抑制细胞凋亡、Bax 和 Bcl-2 蛋白表达,可能在保护肾脏方面发挥重要作用。