摘要
目的探讨胰高糖素样肽-1(GLP-1)拟似物利拉鲁肽对LPS诱导的小鼠肺泡上皮MLE-12细胞损伤的保护作用和对肺表面活性蛋白-A(SP-A)的调节作用。方法将小鼠Ⅱ型肺泡上皮MLE-12细胞分为三组即对照组(Control组)、利拉鲁肽+LPS组(Lir+LPS组)和LPS组。采用MTT法对不同时间点(0、6、12h和24h)MLE-12细胞的活性进行检测。在LPS干预24h后,采用RT-PCR法和western blot法对MLE-12细胞SP-A和甲状腺转录因子-1(TTF-1)的mRNA和蛋白表达进行分析。结果在LPS(0.5μg/ml)干预后,与未干预细胞相比较MLE-12细胞活性呈时间依赖性降低,差异均有显著统计学意义(P<0.05);但与LPS组相比较利拉鲁肽+LPS组细胞在6h、12h和24h细胞活性均较高,差异均有显著统计学意义(P<0.05)。与Control组相比较,在LPS干预12h后MLE-12细胞SP-A和TTF-1的mRNA和蛋白表达均明显降低,差异均有显著统计学意义(P<0.05);且与利拉鲁肽+LPS组细胞相比较,LPS组细胞SP-A和TTF-1的mRNA和蛋白表达下降更加显著,差异均有显著统计学意义(P<0.05)。结论在LPS诱导的小鼠Ⅱ型肺泡上皮MLE-12细胞损伤状态下,GLP-1拟似物利拉鲁肽可以通过促进TTF-1的表达上调SP-A的合成,并对Ⅱ型肺泡上皮细胞产生保护作用。
Objective To explore the value of GLP-1analogue liraglutide in the regulation of surfactant protein-A（SP-A）expression in LPS-induced injury in type II murine alveolar epithelial MLE-12 cells,and its potential mechanism.Methods MLE-12 cells,a cell line derived from murine type II alveolar epithelial cells,were stimulated with LPS（0.5μg/ml）in the presence and absence of GLP-1analogue liraglutide.Then,MTT was used to evaluate the cell viabilities at the corresponding time points（0h,6h,12 hand 24h）.After 12 hours of LPS stimulation,the mRNA and protein expression of SP-A and TTF-1were measured by RT-PCR and western blot.Results The cell viabilities of MLE-12 cells were time-dependent reduced after LPS stimulation.And LPS-reduced MLE-12 cell viabilities were markedly attenuated by liraglutide at each corresponding time points.Then,after 12 hours of LPS stimulation,the mRNA and protein of SP-A and TTF-1 were significantly inhibited by TTF-1.However,LPS-induced down-regulation of SP-A and TTF-1were largely abrogated by liraglutide in MLE-12 cells.Conclusion Our data suggestes that liraglutide could promotes LPS-induced surfactant protein-A（SP-A）expression possibly through up-regulation of TTF-1in type II alveolar epithelial MLE-12 cells.
出处
《西部医学》
2015年第7期981-985,共5页
Medical Journal of West China
基金
重庆市卫生和计生委科技项目(ZY201402030)
