丹参酮ⅡA磺酸钠对舒尼替尼所致H9c2细胞损伤及斑马鱼心脏毒性的保护作用  

Sodium tanshinoneⅡA sulfonate prevents Sunitinib-induced cardiotoxicity in H9c2 cells in vitro and zebrafish in vivo

作　　者：黄晓慧[1] 崔国祯[1] 王亮[1] 李铭源[1] 

机构地区：[1]澳门大学中华医药研究院中药质量研究国家重点实验室,澳门999078

出　　处：《中药药理与临床》2014年第1期37-40,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：澳门科学技术发展基金项目(014/2011/A1)

摘　　要：目的:探讨丹参酮ⅡA磺酸钠(Sodium tanshinoneⅡA sulfonate,STS)对抗肿瘤药物舒尼替尼(Sunitinib malate,Sut)在H9c2细胞和斑马鱼引起的心肌损伤的保护作用。方法:H9c2细胞经药物处理8h后,采用MTT法检测细胞的存活率;用钙离子荧光探针Fura-2 AM观察细胞内游离钙离子的变化;选择发育正常的48hpf(hour post fertilization)斑马鱼胚胎,经药物处理48 h后观察96 hpf斑马鱼心脏形态和功能的变化。结果:10μM舒尼替尼使细胞的活性降低,胞内Ca2+浓度升高;丹参酮ⅡA磺酸钠共同给药组使细胞活性显著提高,10μM时效果最好;同时其也可以抑制胞内Ca2+的升高。在斑马鱼模型中,5μM舒尼替尼心率降低,心包水肿形成,SV-BA/体长的比值增加;100μM丹参酮ⅡA磺酸钠共同给药组对上述损伤均有保护作用。结论:丹参酮ⅡA磺酸钠在一定程度上能拮抗舒尼替尼引起的心脏毒性,其作用机制可能与钙通路有关。Objective： To investigate the protective effects of Sodium tanshinone Ⅱ A sulfonate （STS） against sunitlnib （Sut）-induced cardiac injury in in vitro and in vivo models. Methods：H9c2 cells treated with Sut were used to evaluate cell protective effects of STS. MTr assay was used to observe the cell viability, fura-2/AM to measure intracellttlar calcium level. 48 hour post fertilization （hpf） zebrafish embryos were treated with 5μM Sut in the presence or absence of 100μM STS for 48 h, then morphological and functional changes of embryos hearts were evaluated. Results： H9c2 cells exposured to 10μM Sut leaded to a significant reduction in cell viability and an increase in Ca2＋ level; 10μM STS could promoted cell viability and decrease Ca2＋ level. 48 hpf embryos exposure to 5 μM Sut caused a decrease in heart rate accompanied by an increase in the ratio of SA-BV distance to body length at 96 hpf, which were consistent with the in vitro data. 100μM SIS could increase heart rate, allay pericardial edema and reduce the ration to improve cardiac looping corrected the altered parameters-induced by Sut. Conclusion： STS could prevent Sut-induced H9c2 cell injury and Sut-stimulated cardiac disfunction in zebrafish. The cardioprotective effects of STS perhaps was correlated with calcium homeostasis.

关 键 词：丹参酮ⅡA磺酸钠 心脏保护 舒尼替尼 心脏毒性 

分 类 号：R285[医药卫生—中药学]