多柔比星（DOX）是用于治疗各种癌症和血液恶性肿瘤的药物，由于对组织和器官的毒性作用，其治疗应用有限。这些毒性效应是通过细胞内钙离子调节的改变、细胞应激和氧化损伤的增加以及细胞凋亡的增加而发生的。勒库尼地平（LRD）是一种长效降压药物，具有抗炎、抗凋亡和抗氧化作用。本研究旨在研究LRD对DOX诱导的肺毒性的影响。建立了四个组（对照组、DOX组、DOX+0.5 LRD组和DOX+2 LRD组），共32只大鼠。采用免疫组织化学检测肺组织中的TNF-α水平，并对组织进行了组织病理学检查。通过分光光度法检测总抗氧化状态（TAS）和总氧化应激（TOS），并计算氧化应激指数（OSI）的值来确定氧化应激。通过RT-qPCR评估基因的相对表达水平。结果发现，DOX组的肺组织中炎症和氧化应激标志物以及促凋亡基因水平增加，抗凋亡基因水平减少。此外，组织病理学变化显著增加。尽管没有统计学显著性，但接受0.5 mg/kg LRD的组中炎症、氧化应激和凋亡以及其他组织病理指标均减少。接受2 mg/kg LRD的组中，炎症、氧化应激和凋亡均明显减少，并得到组织学结果的支持。总之，本实验动物模型研究结果表明，LRD对DOX诱导的肺毒性具有改善作用。© 2023. 作者与施普林格自然出版集团德国公司的独家许可下。

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.