西替利嗪对阿霉素所致心脏毒性的保护作用

Protective Effect of Cetririzine on Adriamycin-induced Cardiotoxicity

目的探讨新一代抗组胺药物西替利嗪(Cetririzine,CTZ)对阿霉素(Adriamycin,ADR)所致小鼠心脏毒性的拮抗作用。方法将实验小鼠分为生理盐水对照组,生理盐水+ADR组和CTZ+ADR组,观察接受生理盐水+ADR或CTZ+ADR注射的小鼠心脏组织学变化,心肌细胞凋亡,心肌肌钙蛋白(cTnT)浓度以及小鼠的存活率。结果与生理盐水对照组比较,生理盐水+ADR组小鼠心肌细胞表现为明显的变性、空泡形成及心肌纤维断裂等,心肌细胞TUNEL阳性;CTZ可减轻ADR所致的心脏毒性并抑制ADR所诱导的心肌细胞凋亡;CTZ+ADR组的cTnT显著低于生理盐水+ADR组[(1.03±0.21)vs(8.54±0.93)ng/ml,P<0.01];CTZ+ADR组的小鼠3个月生存率明显高于生理盐水+ADR组(88%vs 64%,P<0.01)。结论CTZ可减轻ADR所致的心脏毒性并改善小鼠生存率。

Objective To investigate the protective effect of antihistamine drug cetririzine （CTZ） on adriamycin-induced cardiotoxicity. Methods Mice were injected intraperitoneally with saline＋ADR, CTZ＋ADR or saline alone （as control） and studied for the histology, apoptosis of the cardiocyte, cardiac troponin （cTnT） level and the overall survival. Results Heart tissues from mice receiving saline plus ADR injection had obvious degeneration, vacuolization of the myocyte, disruption of myofibrils and capillary dilation; The TUNEL staining was positive for myocytes in saline＋ADR group; CTZ could alleviate all these pathological changes and inhibit ADR-induced apoptosis; Serum cTnT level was significantly lower in CTZ＋ADR group （1. 03±0.21） than in saline＋ADR group （8. 54±0.93 ng/ml, P〈0.01） ; The overall survival was also improved in CTZ＋ADR group （88%） as compared with saline＋ADR group （64%, P〈0.01）. Conclusion CTZ antagonizes ADR-induced cardiotoxicity and increased survival rate.