Xiong Jianhua, Ding Binjun, Zhu Wei, Xu Lanlan, Yu Songping
Department of General Medicine, Fuzhou First People's Hospital.
Department of Cardiovascular Medicine, Fuzhou First People's Hospital.
Int Heart J. 2023;64(5):935-944. doi: 10.1536/ihj.23-201.
A certain dosage of cyclophosphamide (CYP) in clinical applications contributes to severe cardiotoxicity. Herein, this study explored the impact of adipose-derived mesenchymal stem cell (AdMSC)-exosomes (Exos) on CYP-induced cardiotoxicity.AdMSCs and AdMSCs-Exos were isolated and identified. CYP was utilized for developing a cardiotoxicity rat model, after which blood was collected and then the serum contents of cardiac injury-related indexes (creatine kinase-MB, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase) were detected with enzyme-linked immunosorbent assay kits. Oxidative stress (OS)-related indicators were measured with the corresponding kits. Myocardial pathological changes and collagen fibrosis were tested with hematoxylin-eosin and Masson staining, and apoptosis-related and autophagy-related proteins in rat cardiac tissues with immunohistochemistry and Western blot assays, respectively.AdMSCs and AdMSCs-Exos were successfully isolated. AdMSCs-Exos could target rat hearts. AdMSCs-Exos improved cardiac function and diminished the content of the cardiac injury-related indexes in CYP rats. In addition, AdMSCs-Exos reduced CYP-induced cardiac fibrosis, OS, apoptosis, and autophagy in rats.AdMSCs-Exos alleviated CYP-induced cardiotoxicity in rats via the repression of OS, apoptosis, and autophagy.
临床应用中一定剂量的环磷酰胺（CYP）会导致严重的心脏毒性。在此，本研究探讨了脂肪间充质干细胞（AdMSC）来源的外泌体（Exos）对CYP诱导的心脏毒性的影响。分离并鉴定了AdMSC和AdMSC-Exos。利用CYP建立心脏毒性大鼠模型，之后采集血液，然后用酶联免疫吸附测定试剂盒检测心脏损伤相关指标（肌酸激酶同工酶MB、乳酸脱氢酶、天冬氨酸氨基转移酶和碱性磷酸酶）的血清含量。用相应试剂盒测量氧化应激（OS）相关指标。用苏木精-伊红染色和Masson染色检测心肌病理变化和胶原纤维化，分别用免疫组织化学和蛋白质印迹法检测大鼠心脏组织中凋亡相关蛋白和自噬相关蛋白。成功分离出AdMSC和AdMSC-Exos。AdMSC-Exos可靶向大鼠心脏。AdMSC-Exos改善了CYP大鼠的心脏功能，降低了心脏损伤相关指标的含量。此外，AdMSC-Exos减少了CYP诱导的大鼠心脏纤维化、OS、凋亡和自噬。AdMSC-Exos通过抑制OS、凋亡和自噬减轻了CYP诱导的大鼠心脏毒性。
