Department of Cellular and Molecular Biology, School of Biology, Damghan University, Damghan, Iran.
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Cell Biochem Biophys. 2024 Sep;82(3):2585-2595. doi: 10.1007/s12013-024-01372-z. Epub 2024 Jul 4.
Oxidative stress hurts the survival of transplanted mesenchymal stem cells (MSCs). Lipopolysaccharide (LPS) preconditioning inhibits apoptotic death in MSCs. Also, Lovastatin's protective effect was reported on MSCs. Here, we investigated the potential of LPS and Lovastatin combination therapy on the survival and proliferation of MSCs. MSCs harvested from adult rats (240-260 g) femur and tibia bone marrow. Third passage MSCs were divided into 6 groups control group, LPS, LPS + Lovastatin (10 and 15 µM), and Lovastatin (10 and 15 µM). Cell survival and proliferation were assessed using an MTT assay 24 h after LPS, Lovastatin, or LPS + Lovastatin treatment. Also, Malondialdehyde (MDA) as a lipid peroxidation marker and antioxidant enzymes such as Glutathione peroxidase (GPX) and Superoxide dismutase (SOD) activity levels evaluated. Finally, the expression level of tumor protein P53 (P53) and octamer-binding transcription factor 4 (OCT4) genes were measured by qRT-PCR test. Lovastatin 10 μM potentiated proliferation and survival of MSCs. It can increase the activity of GPX and SOD. 10 µM Lovastatin could not affect MDA amounts but decreased the expression levels of P53 and Oct4 significantly. Nevertheless, treatment with LPS reduced the survival and proliferation of MSCs, along with a significant reduction in GPX activity. LPS + Lovastatin could increase SOD activity, however, GPX enzyme activity and MSCs proliferation did not change so, and it was not effective. We propose Lovastatin at the dose of 10 µM as a suitable combination agent to increase the survival and proliferation of MSCs in oxidative stress conditions.
氧化应激会损害移植间充质干细胞（MSCs）的存活。脂多糖（LPS）预处理可抑制 MSCs 的凋亡死亡。此外，洛伐他汀已被报道对 MSCs 具有保护作用。在这里，我们研究了 LPS 和洛伐他汀联合治疗对 MSCs 存活和增殖的潜在作用。从成年大鼠（240-260g）股骨和胫骨骨髓中采集 MSCs。第 3 代 MSCs 分为 6 组：对照组、LPS 组、LPS+洛伐他汀（10 和 15μM）组和洛伐他汀（10 和 15μM）组。LPS、洛伐他汀或 LPS+洛伐他汀处理 24 小时后，通过 MTT 测定法评估细胞存活和增殖。还评估了丙二醛（MDA）作为脂质过氧化标志物和谷胱甘肽过氧化物酶（GPX）和超氧化物歧化酶（SOD）等抗氧化酶的活性水平。最后，通过 qRT-PCR 试验测量肿瘤蛋白 P53（P53）和八聚体结合转录因子 4（OCT4）基因的表达水平。10μM 洛伐他汀增强了 MSCs 的增殖和存活。它可以增加 GPX 和 SOD 的活性。10μM 洛伐他汀不能影响 MDA 含量，但能显著降低 P53 和 Oct4 的表达水平。然而，LPS 处理降低了 MSCs 的存活和增殖，同时 GPX 活性显著降低。LPS+洛伐他汀可以增加 SOD 活性，但是 GPX 酶活性和 MSCs 增殖没有变化，因此没有效果。我们建议使用 10μM 的洛伐他汀作为合适的联合剂，以增加氧化应激条件下 MSCs 的存活和增殖。
