Surówka Anna, Żołnierczuk Michał, Prowans Piotr, Grabowska Marta, Kupnicka Patrycja, Markowska Marta, Szlosser Zbigniew, Zagrodnik Edyta, Kędzierska-Kapuza Karolina
Department of Plastic, Endocrine and General Surgery, Pomeranian Medical University, 72-010 Szczecin, Poland.
Department of Vascular Surgery, General Surgery and Angiology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Int J Mol Sci. 2025 Jul 3;26(13):6414. doi: 10.3390/ijms26136414.
Chemokines are low-molecular-weight peptides classified as cytokines with chemotactic properties. The chemokine CXCL13 and its receptor CXCR5 play a significant role in cardiac remodeling, and their expression is markedly increased in experimental models of heart failure. Increased CXCL13 activity is associated with the expression of fibromodulin, a proteoglycan that binds and cross-links collagen fibers. The stressed heart undergoes intensive remodeling, including fibrosis. In our experiment, we investigated the effect of the most commonly used triple immunosuppressive regimens on the expression of the CXCR5 receptor, the chemokine CXCL13, and fibromodulin in rat heart tissue. For this purpose, we used Western blot analysis and ELISA. The study was started on 36 rats divided into 6 groups, which received drugs for a period of 6 months. Our results suggest that the chronic use of calcineurin inhibitors in combination with mycophenolate mofetil is a significant stress factor for the heart, leading to abnormal remodeling of the extracellular matrix. The use of rapamycin may alleviate the negative effects of immunosuppressive therapy on the heart. Our results are consistent with the results of our previous studies and provide a basis for further work aimed at understanding the pathophysiology of the development of changes in the heart with individual immunosuppressive regimens.
趋化因子是一类低分子量肽，归类为具有趋化特性的细胞因子。趋化因子CXCL13及其受体CXCR5在心脏重塑中起重要作用，在心力衰竭实验模型中其表达显著增加。CXCL13活性增加与纤维调节素的表达相关，纤维调节素是一种能结合并交联胶原纤维的蛋白聚糖。应激状态下的心脏会经历包括纤维化在内的强烈重塑。在我们的实验中，我们研究了最常用的三联免疫抑制方案对大鼠心脏组织中CXCR5受体、趋化因子CXCL13和纤维调节素表达的影响。为此，我们采用了蛋白质印迹分析和酶联免疫吸附测定法。该研究以36只大鼠为对象，分为6组，给药6个月。我们的结果表明，长期联合使用钙调神经磷酸酶抑制剂和霉酚酸酯是心脏的一个重要应激因素，会导致细胞外基质异常重塑。使用雷帕霉素可能会减轻免疫抑制治疗对心脏的负面影响。我们的结果与我们之前的研究结果一致，并为进一步研究个体免疫抑制方案下心脏变化的病理生理学提供了基础。
