骨髓间充质干细胞与姜黄素联合治疗改善 MI 大鼠模型心肌血管生成。

Co-treatment with bone marrow-derived mesenchymal stem cells and curcumin improved angiogenesis in myocardium in a rat model of MI.

机构信息

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Mol Biol Rep. 2024 Feb 1;51(1):261. doi: 10.1007/s11033-023-09180-z.

DOI:10.1007/s11033-023-09180-z

PMID:38302805

Abstract

BACKGROUND

The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI).

METHODS AND RESULTS

Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group.

CONCLUSION

Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15 days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.

摘要

背景

间充质干细胞的心脏保护特性和姜黄素（CUR）的治疗潜力已经得到了探索。结合这些方法可能会提高干细胞的有效性并加速愈合。本研究旨在探讨在大鼠心肌缺血（MI）模型中，用姜黄素共同处理骨髓间充质干细胞（BMSCs）对血管内皮生长因子（VEGF）水平的协同作用。

方法和结果

将 65 只雄性大鼠分为四组：G1（健康对照组）、G2（盐酸异丙肾上腺素诱导的 MI）、G3（BMSCs 治疗组）和 G4（CUR 和 BMSCs 共同治疗组）。在 MI 诱导后特定时间点（第 1、7、15 和 21 天）采集血液和组织样本。测量血清乳酸脱氢酶（LDH）、肌酸激酶（CK）、心肌肌钙蛋白 I（cTnI）、天冬氨酸氨基转移酶（AST）、CK-MB 和 VEGF 水平。使用 RT-qPCR 和 Western blot 技术评估 VEGF mRNA 和蛋白表达。通过 H&E 染色和 CD31 免疫荧光染色进行组织病理学评估。CUR-BMSCs 组在第 7 和 15 天 VEGF 表达显著增加，在第 7 天达到峰值。Western blot 分析证实 MI 后第 7 和 15 天 VEGF 蛋白表达增加。ELISA 结果表明，CUR-BMSCs 处理组在第 7 和 15 天血清 VEGF 水平升高，在第 7 天达到最高水平。与未处理的 MI 组相比，治疗组的 LDH、AST、CK、CK-MB 和 cTnI 水平较低。H&E 染色显示，与 MI 组相比，两组治疗组的心肌结构均得到改善，新毛细血管形成增加。