同型半胱氨酸介导的内质网应激对肝细胞脂质代谢的影响

目的： 探讨同型半胱氨酸（Hcy）介导的内质网应激对肝细胞脂质代谢的影响。方法: 5 mmol/L Hcy与HepG2细胞共孵育，检测细胞内Hcy、甘油三酯、胆固醇的含量。高蛋氨酸饮食诱导小鼠高Hcy血症，分析肝细胞内甘油三酯(TGE)、胆固醇(CHO)含量的变化，检测内质网应激蛋白葡萄糖调节蛋白78（GRP-78）、胆固醇调节元件结合蛋白（SREBP-1） mRNA及蛋白表达的变化。结果: 与Hcy孵育后，各时点HepG2细胞内Hcy、脂质（TGE、CHO）含量均显著升高（P<0.05,vs 0 h）。高蛋氨酸饮食小鼠各时点血浆Hcy、肝细胞内TGE、CHO含量均显著高于0周（P<0.05），而血浆TGE、CHO含量升高并不明显（P>0.05,vs 0周）；肝组织内质网应激蛋白GRP-78、SREBP-1 mRNA及其蛋白表达均显著高于0周（P<0.05）。结论: Hcy诱导的内质网应激可致内源性胆固醇调节通路失调，并使肝细胞合成、摄取甘油三酯、胆固醇增加。

Effect of homocysteine-mediated endoplasmic reticulum stress on lipid metabolism in hepatocytes

AIM:To explore the effect of homocysteine (Hcy)-mediated endoplasmic reticulum stress on lipid metabolism in hepatocytes.METHODS: HepG2 cells used in the study were treated with 5 mmol/L Hcy. The concentrations of Hcy, triglycerides (TGE) and cholesterol (CHO) in the cells were measured. In high methionine diet-induced hyperhomocysteinemia C57BL/6 mice, the concentrations of TGE and CHO in hepatocytes were analyzed. The mRNAs and proteins expressions of glucose-regulated protein 78 (GRP-78) and sterol regulatory element binding protein (SREBP-1) were also assessed.RESULTS: The concentrations of Hcy and lipids (TGE, CHO) in HepG2 cells at different time point were elevated after treated with 5 mmol/L Hcy (P<0.05, vs 0 hour). The levels of plasma Hcy and TGE or CHO in hepatocytes of high methionine diet mice at different time point were significantly increased (P<0.05,vs 0 week). However, the TGE and CHO levels in plasma had no change (P>0.05,vs 0 week). The mRNAs and proteins expressions of GRP-78 and SREBP-1 in mice at different time point after high methionine diet were higher than that at 0 week (P<0.05). CONCLUSION: It suggests that Hcy-induced endoplasmic reticulum stress causes dysregulation of the endogenous sterol response pathway, also increases hepatic biosynthesis and uptake of TGE and CHO.