Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu 210000, People's Republic of China.
Drug Des Devel Ther. 2020 Apr 21;14:1561-1569. doi: 10.2147/DDDT.S229520. eCollection 2020.
To elucidate the neuroprotective function of metformin in suppressing propofol-induced apoptosis of HT-22 cells.
HT-22 cells were treated with 0, 10 or 100 μmol/L propofol, followed by determination of their proliferative ability. Subsequently, changes in proliferation and apoptosis of propofol-treated HT-22 cells induced with metformin were assessed. Apoptosis-associated genes in HT-22 cells were detected by Western blot. At last, regulatory effects of Cav-1 on propofol and metformin-treated HT-22 cells were examined.
Propofol treatment dose-dependently decreased proliferative ability and increased apoptosis ability in HT-22 cells, which were partially blocked by metformin administration. Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration. In addition, Cav-1 level in HT-22 cells was regulated by metformin treatment. Notably, metformin reversed propofol-induced apoptosis stimulation and proliferation decline in HT-22 cells via downregulating Cav-1.
In our study, we found that propofol could induce apoptosis of HT-22 cells and metformin could rescue the apoptosis effect regulated by propofol. Then, we found that metformin protects propofol-induced neuronal apoptosis via downregulating Cav-1.
阐明二甲双胍在抑制丙泊酚诱导 HT-22 细胞凋亡中的神经保护作用。
用 0、10 或 100μmol/L 丙泊酚处理 HT-22 细胞，然后测定其增殖能力。接着，评估二甲双胍对丙泊酚处理的 HT-22 细胞增殖和凋亡的影响。用 Western blot 检测 HT-22 细胞中凋亡相关基因。最后，检测 Cav-1 对丙泊酚和二甲双胍处理的 HT-22 细胞的调节作用。
丙泊酚处理剂量依赖性地降低 HT-22 细胞的增殖能力并增加其凋亡能力，而二甲双胍给药部分阻断了这种作用。在丙泊酚处理的 HT-22 细胞中，给予二甲双胍后观察到 Bcl-2 上调和 Bax 下调。此外，丙泊酚处理还调节了 HT-22 细胞中的 Cav-1 水平。值得注意的是，二甲双胍通过下调 Cav-1 逆转了丙泊酚诱导的 HT-22 细胞凋亡刺激和增殖下降。
在本研究中，我们发现丙泊酚可诱导 HT-22 细胞凋亡，而二甲双胍可挽救丙泊酚调节的凋亡作用。然后，我们发现二甲双胍通过下调 Cav-1 来保护丙泊酚诱导的神经元凋亡。
