Zang Zhijun, Li Shujuan, Lin Yuese, Li Xuandi, Li Yunquan, Qin Youzhen, Wang Huishen, Jiang Meihua, Zhu Ling
Department of Infertility and Sexual Medicine, The Third Affiliated Hospital.
Int Heart J. 2015;56(6):651-5. doi: 10.1536/ihj.15-203. Epub 2015 Nov 6.
Adriamycin (ADR) is a potent antineoplastic agent, but long-term treatment is limited by its cumulative, life-threatening cardiomyopathy. Recently, a few reports have shown that pentoxifylline (PTX) might produce cardioprotection in cardiac dysfunction. Here, we investigated the protective effects of PTX on ADR-induced cardiomyopathy in rats. Male rats were randomly assigned either to saline, ADR (adriamycin, 5 mg/kg/week), or A (adriamycin, 5 mg/kg/week) + PTX (pentoxifylline, 50 mg/kg/day) groups. After 3 weeks, these animals were sacrificed and the heart tissue was harvested for histological analysis and assessment of hepatocyte growth factor (HGF) and caspase-3 expression. Histopathological findings showed that PTX can alleviate myocardial damage caused by ADR. Cardiac fibrosis was significantly suppressed in the A+PTX group compared to that in the ADR group. The HGF gene expression was decreased significantly in the ADR group compared with the control group, but was increased in the A+PTX group. Caspase-3 was up-regulated in the ADR group, and down-regulated in the A+PTX group. These results show that treatment with PTX exerts a protective effect against ADR-induced myocardial fibrosis via regulation of HGF and caspase-3 gene expression. PTX may thus represent a useful new clinical tool for the treatment of ADR-induced cardiomyopathy.
阿霉素（ADR）是一种强效抗肿瘤药物，但长期治疗会受到其累积性、危及生命的心肌病的限制。最近，一些报告表明己酮可可碱（PTX）可能对心脏功能障碍产生心脏保护作用。在此，我们研究了PTX对阿霉素诱导的大鼠心肌病的保护作用。将雄性大鼠随机分为生理盐水组、ADR（阿霉素，5毫克/千克/周）组或A（阿霉素，5毫克/千克/周）+PTX（己酮可可碱，50毫克/千克/天）组。3周后，处死这些动物并采集心脏组织进行组织学分析以及评估肝细胞生长因子（HGF）和半胱天冬酶-3的表达。组织病理学结果表明，PTX可减轻阿霉素引起的心肌损伤。与阿霉素组相比，A+PTX组的心脏纤维化得到显著抑制。与对照组相比，阿霉素组的HGF基因表达显著降低，但在A+PTX组中升高。半胱天冬酶-3在阿霉素组中上调，而在A+PTX组中下调。这些结果表明，PTX治疗通过调节HGF和半胱天冬酶-3基因表达对阿霉素诱导的心肌纤维化发挥保护作用。因此，PTX可能是治疗阿霉素诱导的心肌病的一种有用的新临床工具。
