树突状细胞分泌的外泌体对心肌梗死后肝细胞血脂代谢的影响

Effect of exosomes derived from dendritic cells on lipid metabolism of hepatocytes after myocardial infarction

目的:探讨树突状细胞(DCs)所分泌的外泌体(DEXs)对心肌梗死(MI)后肝细胞血脂谱的影响及可能的作用机制。方法:用正常心肌细胞或梗死心肌细胞的上清液刺激小鼠DCs,将DCs分泌的DEXs分别命名为Control-DEX和MI-DEX。用两组DEXs处理肝细胞,酶标测量仪测定肝细胞中脂质的合成和分泌情况。进一步通过蛋白质印迹和实时荧光定量PCR检测肝细胞哺乳动物雷帕霉素靶蛋白(mTOR)-甾醇调节元件结合蛋白(SREBP)通路相关分子的表达。结果:MI-DEX干预肝细胞后,胆固醇和低密度脂蛋白胆固醇(LDL-C)水平显著升高,mTOR-SREBP通路相关分子表达量增加(P<0.05)。使用SREBP抑制剂后,胆固醇的合成和分泌功能随着mTOR-SREBP表达量的降低而下降(P<0.05)。结论:MI-DEX可通过干扰肝细胞中的mTOR-SREBP途径,在MI后肝细胞的血脂代谢中发挥重要作用。

Objective: To investigate the effect of exosomes secreted by dendritic cells (DCs) on the lipid metabolism of hepatocytes after myocardial infarction (MI), and to explore the underlying mechanism. Methods: DCs from mice were stimulated with the supernatants of normal cardiomyocytes or necrotic cardiomyocytes, then the secreted DEXs were named as Control-DEX or MI-DEX, respectively. The hepatocytes were treated with the DEXs secreted from the two groups, then the synthesis and secretion of lipids were determined by the enzyme-labeling measuring instrument. The expression of mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein (SREBP) pathway-related molecules was measured by Western blotting and real-time fluorescent quantitative PCR. Results: After the intervention of MI-DEX, the levels of cholesterol and low density lipoprotein cholesterol (LDL-C) in hepatocytes were enhanced significantly, and the expressions of mTOR-SREBP pathway-related molecules increased ( P <0.05). After the treatment with SREBP inhibitor, the functions of synthesis and secretion of lipids declined with the decreased expression of mTOR-SREBP ( P <0.05). Conclusions: Exosomes derived from DCs may play an important role in the dyslipidemia after MI by interfering the mTOR-SREBP pathway in hepatocytes.