Effect of nicotinamide mononucleotide on doxorubicin-induced cardiac injury in mice

Doxorubicin (DOX) is the cornerstone of chemotherapy regimens for many malignancies, but its clinical usage is limited by severe cardiotoxicity. Accumulating evidence suggest that nicotinamide adenine dinucleotide (NAD+) depletion contributes to DOX-induced cardiotoxicity, making NAD+ boosting an appealing strategy. Nicotinamide mononucleotide (NMN) is an NAD+ precursor that shows promising therapeutic effects in various diseases. To understand the impact of NMN on gene expression in myocardial tissue of DOX-exposed mice, a RNA-seq assay was carried out. Male C57BL/6 mice aged 8 weeks were treated with a single dose of DOX (15 mg/kg, i.p., Pfizer). Sham mice received the same volume of sterile saline. NMN (500 mg/kg, i.p., ApexBio) or saline was given 30 min prior to DOX injection. After 5 days of DOX administration, mice were sacrificed with hearts harvested and subjected to RNA-seq analysis

阿霉素（Doxorubicin, DOX）是多种恶性肿瘤化疗方案的基石性药物，但其临床应用因严重的心脏毒性而受到限制。越来越多的研究证据表明，烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide, NAD+）耗竭参与了阿霉素诱导的心脏毒性进程，因此提升NAD+水平成为极具吸引力的治疗策略。烟酰胺单核苷酸（nicotinamide mononucleotide, NMN）作为NAD+的前体物质，在多种疾病中均展现出具有潜力的治疗效果。为阐明NMN对阿霉素暴露小鼠心肌组织基因表达的影响，本研究开展了RNA测序（RNA-seq）实验。选取8周龄雄性C57BL/6小鼠，单次腹腔注射剂量为15 mg/kg的阿霉素（由辉瑞公司生产）；假手术组小鼠则注射等体积的无菌生理盐水。在阿霉素注射前30分钟，分别给予小鼠腹腔注射NMN（500 mg/kg，ApexBio公司产品）或无菌生理盐水。阿霉素给药5天后，处死小鼠并采集心脏组织，随后进行RNA测序分析。