洛伐他汀联合疗法可增加大鼠骨髓间充质干细胞的存活和增殖,对抗脂多糖的炎症活性。
Lovastatin Combination Therapy Increases the Survival and Proliferation of Rat Bone Marrow-Derived Mesenchymal Stem Cells Against the Inflammatory Activity of Lipopolysaccharide.
发表日期:2024 Jul 04
作者:
Ziba Khosravi, Leila Mirzaeian, Mohammad Taghi Ghorbanian, Farzaneh Rostami
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
氧化应激会损害移植的间充质干细胞(MSC)的存活。脂多糖 (LPS) 预处理可抑制 MSC 的凋亡。此外,洛伐他汀对 MSC 具有保护作用。在这里,我们研究了 LPS 和洛伐他汀联合疗法对 MSC 存活和增殖的潜力。从成年大鼠(240-260 g)股骨和胫骨骨髓中收获 MSC。第三代MSCs分为6组:对照组、LPS组、LPS 洛伐他汀组(10和15μM)、洛伐他汀组(10和15μM)。 LPS、洛伐他汀或 LPS 洛伐他汀处理后 24 小时,使用 MTT 测定评估细胞存活和增殖。此外,还评估了作为脂质过氧化标记的丙二醛 (MDA) 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检测肿瘤蛋白P53(P53)和八聚体结合转录因子4(OCT4)基因的表达水平。洛伐他汀 10μM 增强 MSC 的增殖和存活。它可以增加GPX和SOD的活性。 10μM洛伐他汀不影响MDA含量,但显着降低P53和Oct4的表达水平。然而,LPS 治疗降低了 MSC 的存活和增殖,同时显着降低了 GPX 活性。 LPS 洛伐他汀可以增加SOD活性,但GPX酶活性和MSCs增殖没有变化,效果不佳。我们建议使用 10 µM 剂量的洛伐他汀作为合适的组合药物,以提高 MSC 在氧化应激条件下的存活和增殖。© 2024。作者获得 Springer Science Business Media, LLC(Springer 旗下公司)的独家许可自然。
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.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.