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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 Thirty-two male C57BL / 6J mice, aged 10 weeks, were randomly divided into doxorubicin group (DOX group) and doxorubicin plus sildenafil (DOX + SIL group), 16 mice in each group. In the DOX group, a single intraperitoneal injection of doxorubicin 15 mg / kg was given. In DOX + SIL group, a single intraperitoneal injection of doxorubicin was administered simultaneously with sildenafil 10 mg / kg. After 2 weeks of normal feeding, the viable rat ventricular weight ratio was calculated and the echocardiography was performed. The expression of cGMP in myocardium was detected by enzyme-linked immunosorbent assay (ELISA). Results Sixteen mice survived in DOX group and 16 mice in DOX + SIL group after 2 weeks. The body mass ratio, LVEDD, LVESD, left ventricular ejection fraction (LVEF), shortening of short axis (FS) and cGMP were (0.41 ± 0.15)%, (3.270 ± 0.260) mm, (2.560 ± 0.097) mm, (47.90 ± 0.01)% and (18.53 ± 1.10) (0.32 ± 0.05)%, (2.900 ± 0.180) mm, (2.180 ± 0.120) mm, (53.70 ± 0.16)% and (26.50 ± 1.70)% in DOX + %, (0.940 ± 0.006) mmol / L, respectively. The difference was statistically significant (P <0.05). Conclusion Sildenafil can protect cardiomyopathy induced by doxorubicin, which may improve left ventricular dysfunction induced by doxorubicin in mice through c GMP pathway.