糖尿病癌症患者接受阿霉素(DOX)治疗,一种诱导心脏毒性的有效化疗药物;然而,在患者和动物模型的这种特定疾病进展中,心脏毒性的分子机制是完全未知的。因此,我们设计了一项研究,以了解DOX诱导的糖尿病动物心脏毒性的影响和相关的病理生理机制。将C57BL/6J小鼠分为四个DOX和糖尿病(链脲佐菌素;STZ)治疗组;对照组,STZ,DOX,和DOX+STZ。在第14天,处死动物,超声心动图用于检查心脏功能,收集心脏和血液样本以研究凋亡机制(caspase3,BAX,B细胞白血病/淋巴瘤2(Bcl2),炎症,和心脏重塑。我们的数据显示葡萄糖水平显着增加(p<0.05),凋亡标志物,和单核细胞在凋亡部位的浸润和引发的炎症免疫反应(肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)),在DOX+STZ动物中与对照组和实验组相比。我们还观察到肌原纤维面积显著(p<0.05)增加,纤维化,并且与对照相比,在DOX处理的糖尿病动物中显著降低(p<0.05)心脏功能。总之,我们的数据表明,DOX诱导显著增加的细胞凋亡,纤维化,与非糖尿病动物相比,糖尿病心脏的结构改变。
Diabetic cancer patients were treated with doxorubicin (DOX), a potent chemotherapeutic drug that induces cardiac toxicity; however, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of DOX-induced cardiac toxicity in diabetic animals and the involved pathophysiological mechanisms. C57BL/6 J mice were divided into four DOX- and diabetic (streptozotocin; STZ) - treated groups; control, STZ, DOX, and DOX+STZ. At day 14, animals were sacrificed, echocardiography was used to examine heart function, and heart and blood samples were collected to investigate apoptotic mechanisms (caspase 3, BAX, B-Cell leukemia/lymphoma 2 (Bcl2)), inflammation, and cardiac remodeling. Our data shows a significant (p < 0.05) increase in glucose levels, apoptotic markers, and monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)), in DOX+STZ animals compared with control and experimental groups. We also observed significant (p < 0.05) increase in myofibrillar area, fibrosis, and significantly decreased (p < 0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX induces significantly increased apoptosis, fibrosis, and structural alterations in diabetic hearts compared with non-diabetic animals.