1. Department of Stomatology,the Third Medical Center of PLA General Hospital,Beijing 100039,China; 2. Department of Stomatology,Rocket Force Characteristic Medical Center,Beijing 100088,China; 3. Department of Stomatology,the First Medical Center of PLA General Hospital,Beijing 100853; 4. Department of Stomatology,Fuxing Hospital,Capital Medical University,Beijing 100038,China
摘要目的 探讨生长分化因子11(GDF11)对糖尿病小鼠骨髓间充质干细胞(BMSCs)细胞凋亡的影响及其信号机制。方法 复苏BMSCs并将其分为4组:正常小鼠BMSCs组(Nor),糖尿病小鼠BMSCs组(DB),GDF11干预组(DB+GDF11;GDF11),抑制剂组(DB+GDF11+ LY294002;LY)。各组细胞培养3 d后,台盼蓝染色观察细胞凋亡率。Western blot检测凋亡相关蛋白Bax、Bcl-2和磷酸化(p)-PI3K、p-Akt的表达水平。结果 与正常小鼠BMSCs相比,糖尿病小鼠BMSCs细胞凋亡率显著升高[(36.2±3.3)% vs. (3.1±1.1)%,P＜0.05];GDF11可降低糖尿病小鼠BMSCs细胞凋亡率[(18.9±1.9)% vs. (36.2±3.3)%,P＜0.05],提高Bcl-2/Bax的蛋白表达比[(1.63±0.10) vs. (0.26±0.09);P＜0.05],同时激活PI3K[p-PI3K/PI3K:(0.98±0.08) vs. (0.42±0.11);P＜0.05]/Akt[p-Akt/Akt:(0.94±0.10) vs. (0.32±0.15);P＜0.05]信号通路。而且,当抑制PI3K/Akt信号通路后,GDF11抑制糖尿病小鼠BMSCs凋亡的作用明显减弱[细胞凋亡率:(41.1±3.9)% vs. (18.9±1.9)%,P＜0.05]。结论 GDF11可通过激活PI3K/Ak信号通路抑制糖尿病小鼠BMSCs细胞凋亡。
Abstract：Objective To investigate the effects of GDF11 on apoptosis of BMSCs from diabetic mice and the related mechanism.Methods BMSCs of normal mice (Nor),diabetic mice (DB),DB with GDF11 intervention (GDF11),and DB+GDF11 plus LY294002 (LY) were cultured for 3 days.Trypan blue staining was used to calculate the apoptotic rate,while western blot was used to investigate protein levels of Bax,Bcl-2,phosphorylated (p)-PI3K and p-Akt.Results Compared with Nor,the apoptotic rate of DB was increased [(36.2±3.3)% vs. (3.1±1.1)%,P＜0.05],but GDF11 intervention could reduce the apoptotic rate [(18.9±1.9)% vs. (36.2±3.3)%,P＜0.05],increase Bcl-2/Bax expression[(1.63±0.10) vs. (0.26±0.09);P＜0.05],and activate the PI3K[p-PI3K/PI3K:(0.98±0.08) vs. (0.42±0.11);P＜0.05]/Akt[p-Akt/Akt:(0.94±0.10) vs. (0.32±0.15);P＜0.05]signaling pathway.However,when inhibiting PI3K/Akt signaling pathway,GDF11 had its inhibitory effect on cell apoptosis blunted[apoptotic rate:(41.1±3.9)% vs. (18.9±1.9)%,P＜0.05].Conclusions GDF11 can inhibit the apoptosis of BMSCs from diabetic mice by activating the PI3K/Akt signaling pathway.
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2021, Vol. 32 
