PI3K/Akt信号通路在调控裸鼹鼠体细胞自噬发生中的作用

The naked mole rat have anti-tumor, anti-aging, anti-hypoxia and other biological characteristics. There is an urgent need to study its mechanisms, which is not yet clear, from cells, tissues, and organs. We have demonstrated that cells from naked mole-rats have higher levels of autophagy than the short-lived C57BL/6J mice. Our data reveal that both poor quality nutrition and H2O2-induced neurotoxicity induces autophagy in NMR hepatic stellate cells (HSCs). Cells from naked mole rats have greater sensitivity in activating autophagy processes compared to those from shorter-lived mice in other study. Further studies on naked mole had a variety of special molecular signaling mechanisms to resist excessive proliferation and tumor-producing cells. There is no report whether naked mole rats have special signal mechanism to regulate autophagy up to now. This study is to induced autophagy in cells from naked mole rats with oxygen, starvation and H202, to research the influence of autophagy on PI(3)K/Akt signaling pathway. Meanwhile,chemical reagent intervention was used on PI(3)K/Akt signaling pathway, to research the regultion mechanism of PI(3)K/Akt signaling pathway impact on autophagy in naked mole rat. This sdudy will provide theoretical and experimental evidence for the further research on the sluggish-aging and anti-tumor properties in naked mole rat.

裸鼹鼠同时具有抗肿瘤、抗衰老、耐低氧等生物学特性，但相关机制尚未清楚，亟待从细胞、组织及整体等多层面进行更加深入的研究。前期我们实验证实裸鼹鼠幼鼠自噬水平显著高于同期C57/BL6J小鼠。同时，发现饥饿、低氧、过氧化氢刺激等不利因素刺激均可引发裸鼹鼠肝脏星形细胞自噬水平的改变，另有研究证实裸鼹鼠体细胞自噬调节能力高于短寿命小鼠。此外研究发现裸鼹鼠具有多种特殊的分子信号机制抵抗细胞的过量增殖及肿瘤的产生，但自噬调节是否具有特殊的信号机制目前尚无相关报道。基于此，本研究拟采用缺氧、饥饿以及过氧化氢刺激诱导裸鼹鼠体细胞自噬水平改变，明确其对PI(3)K/Akt信号通路的影响，并干预PI(3)K/Akt信号通路，研究相关信号分子对裸鼹鼠体细胞自噬水平的影响，探索PI(3)K/Akt通路调控裸鼹鼠自噬发生的分子机制，以期为进一步研究裸鼹鼠抗衰老及抗肿瘤特性提供理论和实验依据。

裸鼹鼠同时具有抗肿瘤、抗衰老、耐低氧等生物学特性，但相关机制尚未清楚。我们实验证实裸鼹鼠幼鼠自噬水平显著高于同期C57/BL6J小鼠。饥饿、低氧、过氧化氢刺激等不利因素刺激均可引发裸鼹鼠肝脏星形细胞自噬水平的改变。Poly I:C刺激能够引起裸鼹鼠自噬水平上调，同时，裸鼹鼠的自噬水平的上调亦可能提高肌体的适应能力调节炎症反应，进而起到抵抗Poly I:C损伤的作用。采用缺氧、饥饿以及过氧化氢刺激诱导裸鼹鼠体细胞自噬水平，并检测PI(3)K/Akt信号通路水平，明确PI(3)K/Akt信号通路对自噬影响，并干预PI(3)K/Akt信号通路，研究相关信号分子对裸鼹鼠体细胞自噬水平的影响，探索PI(3)K/Akt通路调控裸鼹鼠自噬发生的分子机制。