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瑞格列奈通过影响细胞凋亡及 Bax、Bcl-2 的表达抑制环孢素 A 诱导的肾小管毒性。

Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression.

出版信息

Turk J Med Sci. 2018 Aug 16;48(4):880-885. doi: 10.3906/sag-1707-44.

DOI:10.3906/sag-1707-44
PMID:30121055
Abstract

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.

MATERIALS AND METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

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。

材料和方法

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。

结果

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。

结论

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。

相似文献

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Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression.瑞格列奈通过影响细胞凋亡及 Bax、Bcl-2 的表达抑制环孢素 A 诱导的肾小管毒性。
Turk J Med Sci. 2018 Aug 16;48(4):880-885. doi: 10.3906/sag-1707-44.
2
Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury.瑞格列奈的抗氧化特性及其对环孢素A诱导的肾小管损伤的保护作用。
Iran J Basic Med Sci. 2016 Jul;19(7):749-54.
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The effect of alpha-melanocyte-stimulating hormone on renal tubular cell apoptosis and tubulointerstitial fibrosis in cyclosporine A nephrotoxicity.α-黑素细胞刺激素对环孢素A肾毒性中肾小管细胞凋亡和肾小管间质纤维化的影响。
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The role of protein kinase CK2 in cyclosporine-induced nephropathy in rats.蛋白激酶CK2在大鼠环孢素诱导的肾病中的作用。
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Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity.茶多酚对环孢素诱导的慢性肾毒性大鼠受试对象肾细胞凋亡的抑制作用。
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Rosuvastatin attenuates inflammation, apoptosis and fibrosis in a rat model of cyclosporine-induced nephropathy.罗苏伐他汀减轻环孢素诱导的肾病大鼠模型中的炎症、细胞凋亡和纤维化。
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Expression of apoptosis regulatory genes in chronic cyclosporine nephrotoxicity favors apoptosis.慢性环孢素肾毒性中凋亡调节基因的表达有利于细胞凋亡。
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Colchicine decreases apoptotic cell death in chronic cyclosporine nephrotoxicity.秋水仙碱可减少慢性环孢素肾毒性中的凋亡性细胞死亡。
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