Lu Xiangyu, Wang Yue, Piao Chenxi, Li Pujun, Cao Lei, Liu Tao, Ma Yajun, Wang Hongbin
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150030, China.
Int J Mol Sci. 2024 Dec 5;25(23):13069. doi: 10.3390/ijms252313069.
The liver plays a crucial role in regulating lipid metabolism. Our study examined the impact of Exosomes derived from adipose mesenchymal stem cells (ADSCs-Exo) on lipid metabolism following liver ischemia-reperfusion injury (IRI) combined with partial hepatectomy. We developed a miniature swine model for a minimally invasive hemi-hepatectomy combined with liver IRI. In this study, we administered PBS, ADSCs-Exo, and adipose-derived stem cells (ADSCs) individually through the portal vein. Before and after surgery, we evaluated various factors including hepatocyte ultrastructure, lipid accumulation in liver tissue, and expression levels of genes and proteins associated with lipid metabolism. In addition, we measured serum and liver tissue levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (CHOL). TEM and oil red O stain indicated a significant reduction in liver steatosis following ADSCs-Exo treatment, which also elevated serum levels of HDL, LDL, TG, and CHOL. Additionally, ADSCs-Exo have been shown to significantly decrease serum concentrations of HDL, LDL, TG, and CHOL in the liver ( < 0.05). Finally, ADSCs-Exo significantly downregulated lipid synthesis-related genes and proteins, including SREBP-1, SREBP-2, ACC1, and FASN ( < 0.05), while upregulating lipid catabolism-related genes and proteins, such as PPAR-α and ACOX1 ( < 0.05). ADSCs-Exo as a cell-free therapy highlights its therapeutic potential in hepatic lipid metabolism abnormalities.
肝脏在调节脂质代谢中起着至关重要的作用。我们的研究考察了脂肪间充质干细胞来源的外泌体（ADSCs-Exo）对肝缺血再灌注损伤（IRI）合并部分肝切除术后脂质代谢的影响。我们建立了一种用于微创半肝切除联合肝IRI的小型猪模型。在本研究中，我们通过门静脉分别给予磷酸盐缓冲液（PBS）、ADSCs-Exo和脂肪来源干细胞（ADSCs）。手术前后，我们评估了各种因素，包括肝细胞超微结构、肝组织中的脂质积累以及与脂质代谢相关的基因和蛋白质的表达水平。此外，我们测量了血清和肝组织中高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、甘油三酯（TG）和总胆固醇（CHOL）的水平。透射电子显微镜（TEM）和油红O染色表明，ADSCs-Exo治疗后肝脂肪变性显著减轻，同时血清中HDL、LDL、TG和CHOL水平也升高。此外，ADSCs-Exo已被证明可显著降低肝脏中HDL、LDL、TG和CHOL的血清浓度（<0.05）。最后，ADSCs-Exo显著下调脂质合成相关基因和蛋白质，包括固醇调节元件结合蛋白-1（SREBP-1）、固醇调节元件结合蛋白-2（SREBP-2）、乙酰辅酶A羧化酶1（ACC1）和脂肪酸合酶（FASN）（<0.05），同时上调脂质分解相关基因和蛋白质，如过氧化物酶体增殖物激活受体-α（PPAR-α）和酰基辅酶A氧化酶1（ACOX1）（<0.05）。ADSCs-Exo作为一种无细胞疗法，凸显了其在肝脏脂质代谢异常中的治疗潜力。
