中文摘要：

目的：2型糖尿病患者体内持续高水平的游离脂肪酸会损伤胰岛β细胞。硫氧还蛋白相互作用蛋白（TXNIP）是内源性的硫氧还蛋白（Trx）抑制蛋白。已知高糖刺激可引起TXNIP表达上调,促进胰岛β细胞凋亡,而游离脂肪酸对TXNIP的影响尚不明确。本实验旨在研究软脂酸对TXNIP表达的影响及机制。方法：在使用不同浓度和不同作用时间的软脂酸充分预实验的基础上,确定使用添加0.5 mmol/L软脂酸的RPMI-1640培养基培养INS-1胰岛细胞24 h,测定细胞TXNIP的表达变化、细胞凋亡情况及可能的调控因子变化。结果：与对照组相比,软脂酸组TXNIP的mRNA水平和蛋白表达量均明显增高（P〈0.01）,软脂酸组凋亡明显高于对照组（P〈0.01）。软脂酸组的核因子κB（NF-κB）蛋白磷酸化水平升高（P〈0.01）,使用不同的NF-κB抑制剂PDTC和SN50均可阻断软脂酸诱导的TXNIP表达上调。结论：饱和脂肪酸软脂酸可通过增加NF-κB磷酸化而上调TXNIP的表达,从而诱导INS-1胰岛细胞凋亡。

英文摘要：

AIM： Chronic exposure to elevated levels of free fatty acids （FFAs） in type 2 diabetes patients is toxic to pancreatic β-cells. Thioredoxin （Trx）-interacting protein （TXNIP）, an endogenous Trx-inhibiting protein, is up-regulated by glucose and is a critical mediator of hyperglycemia-induced β-cell apoptosis in diabetes. However, the effects of FFAs on TXNIP are unknown. In this experiment we observed the effect of palmitate on TXNIP expression in cultured INS-1 islet cells and the pathways involved were analyzed meanwhile.METHODS： After the full basis of preliminary experiment of incubating INS-1 cells with palmitate at different concentrations for different time, INS-1 islet cells were cultured with 0.5 mmol/L palmitate for 24 h. TXNIP expression, cell apoptosis, and expression of transcription factors related to TXNIP transcriptional regulation were determined.RESULTS： Compared with control group, the expression of TXNIP at mRNA and protein levels in palmitate group was significantly up-regulated （P〈0.01）. Cleaved caspase-3/caspase-3 ratio was increased in palmitate group （P〈0.05）, and the apoptosis of the INS-1 cells was also significantly increased （P〈0.01）. Palmitate enhanced the phosphorylation of nuclear factor-κB （NF-κB） （P〈0.01）, and the NF-κB inhibitors, PDTC and SN50, both blocked the palmitate-induced up-regulation of TXNIP expression.CONCLUSION： Saturated fatty acid palmitate enhances the expression of TXNIP. The mechanism of palmitate-induced TXNIP expression may be associa-ted with the increase in NF-κB phosphorylation.