TBHQ激活自噬保护血管内皮细胞脂毒性作用的研究

目的:改善脂毒性引起的血管内皮细胞损伤在心血管疾病防治中发挥重要作用。本研究旨在探讨叔丁基对苯二酚(tert-butylhydroquinone,TBHQ)对脂毒性引起的血管内皮细胞损伤的保护作用。方法:以人脐静脉血管内皮细胞系EA.hy926为研究对象,给予不同浓度的饱和游离脂肪酸及TBHQ进行干预,检测细胞的凋亡情况。采用westernblotting及信号通路阻断技术对TBHQ的作用机制进行研究。结果:给与血管内皮细胞饱和游离脂肪酸进行干预可显著增加细胞死亡(P0.05)。TBHQ显著抑制饱和游离脂肪酸诱导的细胞死亡(P0.05)。激活自噬可显著抑制饱和游离脂肪酸引发的血管内皮细胞脂毒性(P0.05)。此外,TBHQ可显著激活血管内皮细胞的自噬(P0.05),采用自噬抑制剂可阻断TBHQ对脂毒性的保护作用(P0.05)。结论:TBHQ通过激活自噬有效地抑制饱和游离脂肪酸诱导的血管内皮细胞损伤,对于改善或防治高脂血症引起的血管损伤可能具有重要的现实意义。

TBHQ Protects Against Lipotoxicity in Vascular Endothelial Cells via Activating Autophagy

Objective:Improving lipotoxicity-induced injury in vascular endothelial cells plays a critical role in the prevention and cure of cardiovascular diseases. This study was conducted to investigate the protective role of tert-butylhydroquinone (TBHQ) against free fatty acids-induced lipotoxicity.Methods:Human umbilical vein endothelial cell line-Ea.hy926 was employed in this study. Cells were treated with different dose of TBHQ and/or saturated fatty acids (SFAs). The cell death was detected. We also employed western blotting and signal inhibitors to investigate the potential mechanisms.Results:SFAs significantly induced cell death in vascular endothelial cells (P<0.05). TBHQ significantly inhibited SFAs-induced cell death (P<0.05). The activation of autophagy markedly inhibited SFAs-induced lipotoxicity (P<0.05). Additionally, TBHQ significantly activated autophagy in vascular endothelial cells (P<0.05). Inhibiting autophagy markedly blocked the protective role of TBHQ against SFAs-induced cell death (P<0.05).Conclusion:TBHQ protected SFAs-induced cell injury via activating autophagy in vascular endothelial cells. This provided an alternative way in the improving or prevention and cure of hyperlipidemia-induced damage in vascular system.