缺氧诱导HepG2细胞脂类代谢紊乱的作用机制

Mechanism of hypoxia-induced disturbance of lipid metabolism in HepG2 cells

目的探讨缺氧应激诱导肝癌HepG2细胞脂类代谢紊乱的作用机制。方法分别在常氧及缺氧条件下培养HepG2细胞,采用尼罗红和非律平Ⅲ荧光染色分别检测细胞脂质和游离胆固醇蓄积,实时定量PCR和Western blot法检测胆固醇及脂肪酸代谢相关基因的表达。结果与常氧条件相比,缺氧处理后HepG2细胞中脂类物质及游离胆固醇蓄积显著增加,胆固醇及脂肪酸外排、分解代谢相关基因表达受到抑制,脂肪酸摄取途径基因表达增强。结论缺氧应激通过调节脂类摄取、外排及分解途径作用于细胞内脂类代谢紊乱,为缺氧性脂类代谢综合疾病的治疗提供了新思路。

Objective To investigate the underlying for hypoxia-induced disturbance of lipid metabolism in HepG2 cells of hepatic carcinoma. Methods The HepG2 cells were cultured under normoxia and hypoxia conditions at different times. Accumulations of intracellular lipid and free cholesterol were detected by Nile Red and Filipin Ⅲ staining, respectively. The expressions of key genes relevant to cholesterol and lipid metabolism were determined by RQ-PCR and Western blot. Results Compared with normoxia group, the levels of intracellular lipid and free cholesterol were significantly increased, the expressions of key genes relevant to excretion and catabolism of cholesterol and fatty acid were downregulated, while gene expressions in fatty acid uptake pathway were upregulated in hypoxia-treated HepG2 cells. Conclusion Hypoxia can induce dysturbance of lipid metabolism by regulating uptake, catabolism and excretion of fatty acid and cholesterol, which may provide a new clue for the treatment of hypoxic lipid metabolism syndrome.