Qin Jiasheng, Mai Yanxing, Li Yang, Jiang Zesheng, Gao Yi
Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Institute of Regenerative Medicine, Southern Medical University, Guangzhou, Guangdong, P.R. China.
PLoS One. 2017 Apr 28;12(4):e0176652. doi: 10.1371/journal.pone.0176652. eCollection 2017.
Bioartificial liver holds special position in the field of regenerative medicine, and cold environment at 4℃ is widely used for the short storage of both organ and liver cell for later application. However, the disadvantages of such cold storage could influence cell viability and lead to cell apoptosis in different degrees. In this study, we mainly explore the pre-protective effect of mild hypothermia against low temperature (4℃)-induced rat liver cell injury in vitro. Our results indicated that the precondition with mild hypothermia could increase cell viability, such as cell proliferation, LDH regulation and glycogen synthesis ability of liver cell. The precondition also decreased the ROS production and relieved cell apoptosis in liver cells. Compared with the model group, the mitochondrial membrane potential was restored in the mild hypothermia group, as well as the mitochondrial membrane permeability transition pore opening, indicating that the therapeutic mechanism was related to mitochondrial protection. Further analysis showed that PI3K-Akt-GSK3β signal pathway might be associated with the pre-protective effect of mild hypothermia. Thus, our study suggested that the precondition with mild hypothermia hold the protective effect for liver cell in cold environment, and further developed a novel strategy for the storage of liver seed cells, even bioartificial liver.
生物人工肝在再生医学领域具有特殊地位，4℃的低温环境被广泛用于器官和肝细胞的短期保存以备后续应用。然而，这种冷藏的缺点可能会影响细胞活力并导致不同程度的细胞凋亡。在本研究中，我们主要探讨轻度低温对体外低温（4℃）诱导的大鼠肝细胞损伤的预保护作用。我们的结果表明，轻度低温预处理可以提高细胞活力，如肝细胞的增殖、乳酸脱氢酶调节和糖原合成能力。预处理还减少了活性氧的产生并减轻了肝细胞的凋亡。与模型组相比，轻度低温组的线粒体膜电位得以恢复，线粒体膜通透性转换孔开放情况也有所改善，表明其治疗机制与线粒体保护有关。进一步分析表明，PI3K-Akt-GSK3β信号通路可能与轻度低温的预保护作用有关。因此，我们的研究表明，轻度低温预处理对寒冷环境中的肝细胞具有保护作用，并进一步为肝种子细胞甚至生物人工肝的保存开发了一种新策略。
