FGF-21与罗格列酮钠对棕榈酸诱导的胰岛细胞株凋亡的保护作用及机制研究

Protective Effect of Fibroblast Growth Factors-21 and Rosiglitazone Sodium on Palmitic Acid-induced Apoptosis in HIT-T15 Cells

目的探讨成纤维细胞生长因子-21(FGF-21)和罗格列酮钠(RO)对棕榈酸(PA)诱导的HIT-T15胰岛细胞凋亡的保护作用和机制。方法①0.25、0.50和1.00 mmol/L的PA干预HIT-T15细胞24 h,流式细胞仪检测细胞凋亡。②在0.50 mmol/L的PA中分别加入FGF-21〔12.50 nmol/L(A)、25.00 nmol/L(B)、50.00 nmol/L(C)〕、1μmol/L RO及3个不同浓度的FGF-21与RO联合,检测细胞凋亡,免疫细胞化学法、Western blot检测各组细胞磷酸化c-jun氨基末端激酶(p-JNK)的表达。结果①PA组细胞凋亡高于对照组(P<0.05)。②FGF-21 A、B、C组能明显降低0.50 mmol/L PA诱导的凋亡(P<0.05),但凋亡率高于对照组(P<0.05)。FGF-21与RO联合干预组的细胞凋亡低于PA组(P<0.05)。联合干预组的细胞凋亡低于单用FGF-21组(P<0.05)。③0.50 mmol/L PA组的p-JNK蛋白表达高于对照组(P<0.05)。不同浓度FGF-21组的p-JNK的表达均低于PA组(P<0.05)。FGF-21与RO联合干预组的p-JNK均低于PA组(P<0.05)。联合干预组p-JNK的表达低于单用FGF-21组(P<0.05)。结论①PA可剂量依赖性的诱导HIT-T15胰岛细胞的凋亡。②FGF-21能抑制PA诱导的HIT-T15胰岛细胞株的凋亡,此机制可能是抑制了p-JNK的表达,并且与RO有协同作用。

Objective To investigate the protective effect of fibroblast growth factors-21（FGF-21）and rosiglitazone sodium（RO） on palmitic acid-induced apoptosis in HIT-T15 cells.Methods ① HIT-T15 cells were treated with 0.25 mmol/L,0.50 mmol/L and 1.00 mol/L of palmitic acid for 24 hours.② FGF-21（12.50 nmol/L（A）,25.00 nmol/L（B）,50.00 nmol/L（C））,or 1 μmol/L of RO,or a combination of the two were added to the cells treated with 0.50 mmol/L of palmitic acid.Cell apoptosis was measured by flow cytometer.Phosphorylation-c-Jun N-terminal kinases（p-JNK）was detected by immuocytochemistry and Western blot.Results ① The cells treated with palmitic acid has significantly higher apoptosis rates than controls（P〈0.05）.② FGF-21 reduced apoptosis rates induced by palmitic acid（P〈0.05）.But the apoptosis rates remained higher than controls（P〈0.05）.A combination of FGF-21 and RO further reduced the apoptosis rates compared with FGF-21 alone（P〈0.05）.③ The cells treated with palmitic acid had higher expression of p-JNK than controls（P〈0.05）.FGF-21 and a combination of FGF-21 and RO reduced the expression of p-JNK in cells treated with palmitic acid（P〈0.05）.Conclusion ① Palmitic acid induces apoptosis in HIT-T15 cells in a dose dependent way.② The expression of p-JNK induced by palimitic acid is reduced by FGF-21 and the combination of FGF-21 and RO.