利拉鲁肽下调游离脂肪酸作用下βTC3细胞PERK的表达

The Down-regulation Effect of Liraglutide(Lira) on the Expression of Double-stranded RNA-dependent Protein Kinase-like Endoplasmic Reticulum Kinase(PERK) in βTC3 Cells Induced by Free Fatty Acids(FFA)

目的:探讨游离脂肪酸(FFA)作用下胰岛βTC3细胞双链RNA依赖性蛋白样内质网激酶(PERK)的表达以及利拉鲁肽(Lira)对其表达的干预作用。方法:以βTC3细胞为研究对象,分为对照组和FFA组(0.125,0.25,0.5及1 mmol/L)孵育24 h,Westernblot方法检测PERK的表达。然后,分为对照组,FFA组,和FFA+Lira组(0.5 mg/L和1 mg/L),Lira预孵育6 h后,1 mmol/L FFA继续孵育24 h,Western blot检测PERK的表达。结果:①不同浓度FFA孵育24 h后,与对照组相比,1 mmol/L FFA组PERK表达增加(P<0.05)。②与1 mmol/L FFA组相比,0.5mg/L Lira+1 mmol/L FFA和1 mg/L Lira+1 mmol/L FFA组PERK表达减少(P<0.05),两组之间有统计学差异(P<0.05)。结论:FFA作用能够上调βTC3细胞PERK的表达,而Lira在一定程度上逆转FFA水平异常导致的βTC3细胞PERK表达上调,减轻内质网应激反应。

Objective： To investigate the expression of PERK in βTC3 cells exposed to different concentrations of FFA and the intervention effect of Lira on the expression of double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase（PERK） induced by FFA.Methods： βTC3 cells were treated with different concentrations of FFA（0,0.125,0.25,0.5 and 1.0 mmol/L）.Western Blot analysis was used to determine the expression of PERK in βTC3 cells after 24 hours.Afterwards,βTC3 cells were prein-cubated with different concentrations of Lira（0,0,0.5,1 mg/L）for 6 hours,and different concentrations of FFA（0,1,1,1 mmol/L） were then added and the cells were incubated for another 24 hours.The expression of PERK was detected.Results： ①After the cells were in-cubated with FFA of different concentrations for 24 hours,compared with the control group,the expression of PERK in βTC3 cells in the group with 1 mmol/L FFA increased（P〈0.05）.②Compared with that in the group with 1 mmol/L FFA,the expression of PERK de-creased（P〈0.05） in the group with 0.5 mg/L Lira＋1 mmol/L FFA and the group with 1 mg/L Lira＋1 mmol/L FFA,and there was statisti-cal difference between the two groups（P〈0.05）.Conclusion： The expression of PERK in βTC3 cells is up-regulated by administration of FFA of certain concentration,while Lira can reverse this response to some extent,partly inhibiting endoplasmic reticulum stress.