Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan.
J Pak Med Assoc. 2023 Feb;73(Suppl 1)(2):S3-S8. doi: 10.47391/JPMA.AKUS-01.
To determine the effect of the pre-treatment of mesenchymal stem cells (MSCs) with minocycline on the expression of antioxidant genes and cardiac repair post myocardial infarction (MI) in rats.
Rat bone marrow derived MSCs were used in the study. Cytotoxicity of minocycline in MSCs was determined using JC1 assay to identify a safe drug dose for further experiments. The MSCs were pre-treated with 1.0 µM minocycline for 24 hours and then treated with hydrogen peroxide (H2O2), after that mRNA was isolated and the expression levels of antioxidant genes including peroxiredoxin, glutathione peroxidase, and superoxide dismutase were determined. Finally, minocycline pre-treated MSCs were used to treat rats induced with MI by the ligation of left anterior descending coronary artery. The cardiac function was evaluated at two and four weeks post MI using echocardiography.
At 1.0 µM concentration, minocycline was found to be safe for MSCs and used for subsequent experiments. Minocycline pre-treatment was found to up regulate several antioxidant genes in oxidatively stressed MSCs. Furthermore, minocycline pre-treated MSCs displayed greater improvement in cardiac left ventricular function at two and four-weeks post MI as compared to untreated rats.
Pre-treatment of MSCs with minocycline enhances the expression of antioxidant genes and promotes their capability to repair cardiac function after MI.
确定骨髓间充质干细胞（MSCs）预先用米诺环素处理对大鼠心肌梗死后抗氧化基因表达和心脏修复的影响。
本研究使用大鼠骨髓来源的 MSCs。使用 JC1 测定法测定米诺环素对 MSCs 的细胞毒性，以确定用于进一步实验的安全药物剂量。将 MSCs 用 1.0 μM 米诺环素预处理 24 小时，然后用过氧化氢（H2O2）处理，然后分离 mRNA，并测定抗氧化基因（包括过氧化物酶、谷胱甘肽过氧化物酶和超氧化物歧化酶）的表达水平。最后，用预先用米诺环素处理的 MSCs 治疗通过结扎左前降支冠状动脉诱导的 MI 大鼠。MI 后 2 周和 4 周使用超声心动图评估心脏功能。
在 1.0 μM 浓度下，米诺环素对 MSCs 安全，用于后续实验。发现米诺环素预处理可上调氧化应激 MSCs 中的几种抗氧化基因。此外，与未处理的大鼠相比，米诺环素预处理的 MSCs 在 MI 后 2 周和 4 周时心脏左心室功能的改善更为明显。
MSCs 预先用米诺环素处理可增强抗氧化基因的表达，并促进其在 MI 后修复心脏功能的能力。
