小鼠骨髓间充质干细胞自噬与衰老的关系

目的 探讨小鼠骨髓间充质干细胞（BM-MSCs）自噬与衰老的关系。方法 通过体外分离培 养年轻组小鼠（8 周龄）和老年组小鼠（18 个月龄）BM-MSCs，流式细胞术检测细胞表型，TUNEL 染色检 测细胞凋亡，ELISA 试剂盒检测BM-MSCs 分泌蛋白VEGF、bFGF、IGF-1、HGF 的表达，Western blot 检 测自噬相关蛋白LC3- Ⅰ、LC3- Ⅱ、Beclin 1、ATG12-5、p62 及信号通路蛋白p-Akt、Akt、p-mTOR、 mTOR 的表达。结果 与年轻组比较，老年组BM-MSCs 凋亡增加（P <0.05），分泌功能下降（P <0.05），自 噬相关蛋白LC3- Ⅰ、LC3- Ⅱ、Beclin 1、ATG12-5 表达水平下降（P <0.05），相反p62 蛋白表达水平升高 （P <0.05），自噬信号通路相关蛋白p-Akt、Akt、p-mTOR、mTOR 表达升高。结论 老年小鼠BM-MSCs 凋亡增加，自噬活性及旁分泌功能下降。

Correlation between autophagy of bone marrow mesenchymal stem cells and aging in mice

Objective To investigate the effect of autophagy of bone marrow mesenchymal stem cells (BMMSCs) on the aging process in mice. Methods BM-MSCs were isolated from the bone marrow of young (8 w) and elderly (18 m) mice respectively. BM-MSCs were cultivated in vitro , and characterized using flow cytometry. Apoptosis was detected by TUNEL staining. Meanwhile, the expressions of VEGF, bFGF, IGF-1 and HGF in the BM-MSCs were detected by ELISA kits. The expressions of autophagy-related proteins (such as LC3-I, LC3-II, Beclin 1, ATG12-5 and p62) and signal pathway proteins (such as p-Akt, Akt, p-mTOR and mTOR) were evaluated by Western blot. Results Compared with the young group, the apoptosis in the aged group was significantly increased (P < 0.05), while the secretory function was decreased (P < 0.05). Furthermore, the expressions of LC3-I, LC3-II, Beclin 1 and ATG12-5 were decreased (P < 0.05), whereas p62 was increased (P < 0.05) in the aged group. The expressions of p-Akt, Akt, p-mTOR and mTOR were increased in the aged group. Conclusions In aged mice, apoptosis of BM-MSCs increases, paracrine function and autophagy activity decrease.