GABA对高糖诱导氧化损伤的RIN-m5f细胞的保护作用和机制

Effect of GABA on RIN-m5f Cells in High Glucose－Induced Oxidative Injury Model

摘要:

GABA在胰腺中能够发挥保护作用,但是其具体的作用机制尚不明确。为了确定GABA是否对胰岛β细胞具有抗氧化、抗凋亡以及促进胰岛素分泌的作用,作者采用高糖(44 mmol/L)诱导建立细胞氧化损伤模型,通过测定细胞存活率、细胞ROS生成量、细胞抗氧化酶活、丙二醛含量、胰岛素分泌量以及相关基因水平,分析探讨不同浓度的GABA(10、50、100 μmol/L)对高糖诱导氧化损伤的RIN - m5f细胞的保护作用。结果表明,GABA可以提高RIN - m5f细胞的存活率,降低ROS生成量,显著促进SOD和GSH - Px的活力,降低MDA的浓度,促进胰岛素分泌,提高Nrf2和Bcl - 2的mRNA水平,并降低GSK - 3β和Bax的mRNA水平。而且现出的这些作用存在量效关系。GABA的保护作用可能通过抑制GSK - 3β,进一步抑制Bax并激活Nrf2和Bcl - 2等关键因子从而实现。因此,GABA对RIN - m5f具有抗氧化、抗凋亡以及促进胰岛素分泌的作用。

Abstract:

Oxidative injury was induced by high glucose. Cell viability,production of ROS,the activity of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px),malondialdehyde(MDA) content,insulin secretion and related genes level were measured to investigate the effect of different concentration of GABA(10、50、100 μmol/L) on RIN-m5f cells in high glucose-induced oxidative injury model. The results demonstrated that GABA improved the cell viability,reduced ROS ptoduction,significant enhanced the activity of SOD and GSH-Px,lowered the MDA content,ptomoted insulin secretion,increased the mRNA level of Nrf2 and Bcl-2,and decrease the mRNA level of GSK-3β and Bax. It follows that GABA possesses the anti-apoptosis and anti-oxidative protective effect on RIN-m5f,and this ptotection may be achieved by inhibit GSK-3β and then inhibit Bax,and activate several key factors such as Nrf2 and Bcl-2.