西地那非对阿霉素心肌病的保护作用的实验研究  

Experimental study of protective effect of sildenafil on doxorubicin induced cardiomyopathy

作　　者：张新莉[1] 刚丽[1] 张健[2] ZHANG Xin-li GANG Li ZHANG Jian(EICU Ward, Zhongshan University Affiliated Zhongshan Hospiial, Dalian 116000, China)

机构地区：[1]大连大学附属中山医院EICU病房,116000 [2]大连大学附属中山医院心内科,116000

出　　处：《中国实用医药》2017年第27期197-198,共2页China Practical Medicine

摘　　要：目的探讨西地那非对小鼠阿霉素所致心肌病的保护作用及其机制。方法选取32只雄性10周龄C57BL/6J小鼠,随机分为阿霉素组(DOX组)与阿霉素加西地那非组(DOX+SIL组),每组16只。DOX组单一腹腔内注射阿霉素15 mg/kg;DOX+SIL组单一腹腔内注射阿霉素的同时,给予西地那非10 mg/kg灌胃。正常饲养2周后计算存活小鼠心室体重比,并对其进行心脏超声检查;采用酶联免疫吸附试验(ELISA)法检测心肌组织中环磷酸鸟苷(c GMP)的表达情况。结果 2周后DOX组存活16只小鼠,DOX+SIL组存活16只小鼠,DOX组心室体重比、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)和短轴缩短率(FS)、c GMP分别为(0.41±0.15)%、(3.270±0.260)mm、(2.560±0.097)mm、(47.90±0.01)%、(18.53±1.10)%、(0.051±0.006)mmol/L,与DOX+SIL组的(0.32±0.05)%、(2.900±0.180)mm、(2.180±0.120)mm、(53.70±0.16)%、(26.50±1.70)%、(0.940±0.006)mmol/L比较差异均具有统计学意义(P<0.05)。结论西地那非对阿霉素所致心肌病具有保护作用,可能通过c GMP通路,明显改善阿霉素诱导的小鼠左心室功能障碍。Objective To investigate the protective effect of sildenafil on doxorubicin induced cardiomyopathy in mice and its mechanism. Methods A total of 32 male 10 week old C57BL/6J mice were randomly divided into doxombicin group （DOX group） and doxorubicin and sildenafil group （DOX±SIL group）, with 16 mice in each group. DOX group received single intraperitoneal injection of doxorubicin 15 mg/kg, and DOX±SIL group received gavage administration of sildenafil 10 mg/kg, on the basis of intraperitoneal injection of doxorubicin. After 2 weeks of normal feeding, ventricular weight ratio of the surviving mice was calculated and the heart ultrasonic examination was performed. The expression of cyclic guanosine monophosphate （cGMP） in the myocardium was detected by enzyme linked immunosorbent assay （ELISA）. Results After 2 weeks, DOX group had survived mice, and DOX±SIL group had survived mice. DOX group had statistically significant difference in ventricular weight ratio, left ventricular end diastolic diameter （LVEDD）, left ventricular end systolic diameter （LVESD）, left ventricular ejection fraction （LVEF） and fraction shortening （FS） and cGMP respectively as （0.41 ± 0.15）%, （3.270 ± 0.260）mm, （2.560 ± O.097）mm, （47.90 ± 0.01）%, （18.53 ± 1.10）% and （0.051 ± 0.006）mmol/L, comparing with （0.32 ± 0.05）%, （2.900 ± 0.180） mm, （2.180 ± 0.120） mm, （53.70 ± 0.16）%, （26.50 ± 1.70）% and （0.940 ± 0.006）mmol/L in DOX±SIL group （P〈0.05）. Conclusion Sildenafil shows protective effect for doxorubicin induced cardiomyopathy, ang it can significantly improve doxorubicin induced left ventricular dysfunction in mice through the cGMP pathway.

关 键 词：阿霉素 心肌病 西地那非 纤维化 

分 类 号：R965[医药卫生—药理学]