Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway (Retracted article. See vol. 742, 2023)
Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway (Retracted article. See vol. 742, 2023)
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DOI：
10.1016/j.abb.2010.07.012
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发表时间：
2010-10-15
影响因子：
3.9
通讯作者：
Huang, Heqing
中科院分区：
文献类型：
--
作者：
Lan, Tian;Shen, Xiaoyan;Huang, Heqing
小檗碱（BBR）以前被发现对实验性糖尿病大鼠的肾损伤有有益的作用。然而，这些影响背后的机制尚未完全了解。鞘氨醇激酶-1-磷酸鞘氨醇（SphK-S1 P）信号通路参与了糖尿病肾病（DN）的发病机制。本研究旨在探讨BBR对四氧嘧啶诱导的糖尿病肾病小鼠肾脏损伤及SphK-S1 P信号通路激活的影响。四氧嘧啶诱导的糖尿病小鼠经口给予BBR（300 mg/kg/天）或溶剂12周。BBR抑制糖尿病小鼠空腹血糖、肾/体重比、血尿素氮、血清肌酐和24小时尿蛋白的增加。它还防止肾肥大、TGF-β 1合成、FN和Col IV积累。此外，BBR还下调了SphK 1的染色、活性、mRNA和蛋白水平以及S1 P的产生。提示BBR抑制糖尿病小鼠肾脏SphK-S1 P信号通路的激活是其部分发挥肾脏保护作用的新机制。(C)2010年爱思唯尔公司All rights reserved.
Berberine (BBR) was previously found to have beneficial effects on renal injury in experimental diabetic rats. However, the mechanisms underlying the effects are not fully understood. Sphingosine kinase-Sphingosine 1-phosphate (SphK-S1P) signaling pathway has been implicated in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to investigate the effects of BBR on renal injury and the activation of SphK-S1P signaling pathway in alloxan-induced diabetic mice with nephropathy. Alloxan-induced diabetic mice were treated orally with BBR (300 mg/kg/day) or vehicle for 12 weeks. BBR inhibited the increases in fasting blood glucose, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. It also prevented renal hypertrophy, TGF-beta 1 synthesis, FN and Col IV accumulation. Moreover, BBR down-regulated the elevated staining, activity and levels of mRNA and protein of SphK1, and S1P production as well. These findings suggest that the inhibitory effect of BBR on the activation of SphK-S1P signaling pathway in diabetic mouse kidney is a novel mechanism by which BBR partly exerts renoprotective effects on DN. (C) 2010 Elsevier Inc. All rights reserved.