软脂酸对INS-1胰岛细胞TXNIP表达的影响

发布时间：2018-07-29 19:03

【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(P0.01),软脂酸组凋亡明显高于对照组(P0.01)。软脂酸组的核因子κB(NF-κB)蛋白磷酸化水平升高(P0.01),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。
[Abstract]:Objective the high level of free fatty acids in patients with type 2 diabetes can damage islet 尾 cells. Thioredoxin interacting protein (TXNIP) is an endogenous thioredoxin (Trx) inhibitor. It is known that high glucose stimulation can induce the up-regulation of TXNIP expression and promote the apoptosis of islet 尾 cells, but the effect of free fatty acids on TXNIP is not clear. The purpose of this study was to investigate the effect of palmitate on TXNIP expression and its mechanism. Methods: on the basis of sufficient pre-experiment of different concentrations and different time of action of palmitic acid, RPMI-1640 medium supplemented with 0.5 mmol/L palmitic acid was used to culture INS-1 islet cells for 24 h, and the expression of TXNIP was measured. Apoptosis and possible regulatory factors. Results: compared with the control group, the mRNA level and protein expression of TXNIP in the palmitic acid group were significantly higher than those in the control group (P0.01), and the apoptosis in the palmitic acid group was significantly higher than that in the control group (P0.01). The phosphorylation level of nuclear factor 魏 B (NF- 魏 B) protein was increased in the palmitate group (P0.01). PDTC and SN50, different NF- 魏 B inhibitors, could block the up-regulation of TXNIP expression induced by palmitate. Conclusion: saturated fatty acid palmitate can up-regulate the expression of TXNIP by increasing the phosphorylation of NF- 魏 B, thus inducing apoptosis of INS-1 islet cells.
【作者单位】：山西医科大学生理学教研室;山西医科大学转化医学研究中心;
【基金】：国家自然科学基金资助项目(No.30800399) 山西省重点实验室建设项目(No.2014011049-12) 山西医科大学科技创新基金资助项目(No.01201406)
【分类号】：R363;;R587.1

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