Background

Bone marrow mesenchymal stem cells (BMSCs) may be a promising target in the treatment of myocardial infarction (MI). However, the underlying molecular mechanisms of BMSC therapy remain unclear.

Objective

This study sought to evaluate the efficacy of direct intramyocardial transplantation of BMSCs in a mouse model of MI.

Methods

Mouse BMSCs were transfected with small interfering RNA or overexpression plasmid targeting TXNIP. The viability, proliferation, and apoptosis of BMSCs after hypoxia treatment were detected by MTT method, EdU analysis, and flow cytometry, respectively. A mouse model of MI was constructed, after which BSMCs were injected intramyocardially immediately. Cardiac ultrasound, HE staining, TUNEL staining and ELISA, IHC analysis, and Western blot were adopted to evaluate the effects of BSMC therapy on cardiac function, myocardial inflammation, and fibrosis in mice.

Results

In vitro experiments reported that ablating TXNIP increased viability and inhibited apoptosis of hypoxia-treated BMSCs while overexpressing TXNIP did the opposite. In vivo results stated that BSMCs improved cardiac function, myocardial inflammation, and fibrosis after MI, which was further improved by silencing TXNIP but reversed by overexpressing TXNIP. Meanwhile, in vivo cell tracking experiments showed that the retained BMSCs in the myocardium decreased after transplantation, and TXNIP depletion promoted the survival of BMSCs in MI mice, whereas TXNIP overexpression did the opposite.

Conclusion

In conclusion, BMSC transplantation improves cardiac function, myocardial inflammation, and fibrosis after MI by regulating the TXNIP/NLRP3 pathway.

中文翻译：

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骨髓间充质干细胞移植通过调节TXNIP/NLRP3通路介导的炎症和纤维化保护大鼠心肌梗死

背景

骨髓间充质干细胞（BMSCs）可能是治疗心肌梗死（MI）的一个有前景的靶标。然而，BMSC 治疗的潜在分子机制仍不清楚。

客观的

本研究旨在评估在 MI 小鼠模型中直接心肌内移植 BMSC 的功效。

方法

用靶向 TXNIP 的小干扰 RNA 或过表达质粒转染小鼠 BMSC。分别采用MTT法、EdU分析和流式细胞术检测缺氧处理后BMSCs的活力、增殖和凋亡。构建小鼠心肌梗死模型，立即将BSMCs注射至心肌内。采用心脏超声、HE染色、TUNEL染色以及ELISA、IHC分析和Western blot评价BSMC治疗对小鼠心功能、心肌炎症和纤维化的影响。

结果

体外实验表明，消除 TXNIP 会增加缺氧处理的 BMSC 的活力并抑制细胞凋亡，而过表达 TXNIP 则会产生相反的效果。体内结果表明，BSMC 改善了 MI 后的心脏功能、心肌炎症和纤维化，通过沉默 TXNIP 可以进一步改善这种情况，但通过过度表达 TXNIP 可以逆转这种情况。同时，体内细胞追踪实验表明，移植后心肌中保留的BMSCs减少，TXNIP耗竭促进MI小鼠BMSCs的存活，而TXNIP过表达则相反。

结论

总之，BMSC移植通过调节TXNIP/NLRP3通路改善MI后的心功能、心肌炎症和纤维化。