Protective effect of cyanidin-3-O-glucoside on neonatal porcine islets
Protective effect of cyanidin-3-O-glucoside on neonatal porcine islets
复制标题
花青素-3-O-葡萄糖苷对新生猪胰岛的保护作用。
DOI：
10.1530/joe-17-0141
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Rayat, Gina R.
中科院分区：
文献类型：
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作者：
Li, Chao;Yang, Bin;Rayat, Gina R.
在分离和移植过程中，氧化应激是胰岛损伤和功能障碍的主要原因。花青素-3-O-葡萄糖苷(C3G)广泛存在于各种水果和蔬菜中，尤其是杨梅中，具有很强的抗氧化性。在本研究中，我们确定了C3G是否能在体外保护新生猪胰岛(NPI)免受过氧化氢(H_2O_2)损伤，并促进NPI在糖尿病小鼠中的功能。结果表明，C3G对NPI无毒害作用，对H_2O_2诱导的NPI有保护作用。在移植前后，经C3G治疗的NPI患者的胰岛组织中，血红素氧合酶-1(HO1)基因的表达显著高于未经治疗的胰岛组织(P<；0.05)。Western印迹分析显示，经C3G处理的NPI细胞内磷酸化细胞外信号调节激酶1/2(ERK1/2)和磷脂酰肌醇3-激酶(PI3K/Akt)蛋白水平较未经处理的胰岛显著增加。C3G诱导核红系2相关因子2(NRF2)核移位，HO1蛋白显著升高。接受C3G治疗的NPI患者与未接受治疗的胰岛患者相比，接受C3G补充饮用水的患者血糖正常的时间更早。在移植后5-10周，与接受未经处理的胰岛的小鼠相比，接受C3G处理的胰岛并补充或不补充C3G水的小鼠的血糖水平显著降低。与接受C3G处理的胰岛的小鼠相比，接受C3G处理的NPI和补充C3G的饮用水的小鼠在移植后7周和8周的血糖水平显著降低(P<；0.05)。这些结果表明，C3G通过激活ERK1/2和PI3K/AKT诱导的NRF2介导的HO1信号通路，对NPI有一定的治疗作用。
Oxidative stress is a major cause of islet injury and dysfunction during isolation and transplantation procedures. Cyanidin-3-O-glucoside (C3G), which is present in various fruits and vegetables especially in Chinese bayberry, shows a potent antioxidant property. In this study, we determined whether C3G could protect neonatal porcine islets (NPI) from reactive oxygen species (H2O2)-induced injury in vitro and promote the function of NPI in diabetic mice. We found that C3G had no deleterious effect on NPI and that C3G protected NPI from damage induced by H2O2. Significantly higher hemeoxygenase-1 (HO1) gene expression was detected in C3G-treated NPI compared to untreated islets before and after transplantation (P < 0.05). Western blot analysis showed a significant increase in the levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K/Akt) proteins in C3G-treated NPI compared to untreated islets. C3G induced the nuclear translocation of nuclear erythroid 2-related factor 2 (NRF2) and the significant elevation of HO1 protein. Recipients of C3G-treated NPI with or without C3G-supplemented drinking water achieved normoglycemia earlier compared to recipients of untreated islets. Mice that received C3G-treated islets with or without C3G-supplemented water displayed significantly lower blood glucose levels at 5-10 weeks post-transplantation compared to mice that received untreated islets. Mice that received C3G-treated NPI and C3G-supplemented drinking water had significantly (P < 0.05) lower blood glucose levels at 7 and 8 weeks post-transplantation compared to mice that received C3G-treated islets. These findings suggest that C3G has a beneficial effect on NPI through the activation of ERK1/2-and PI3K/AKT-induced NRF2-mediated HO1 signaling pathway.