肥大细胞脱颗粒稳定剂对SD大鼠心肌梗死后不良心室重构的影响

目的阐明心脏肥大细胞对心肌梗死后心功能的影响,探讨心脏肥大细胞在心肌梗死心室重构中的作用。方法结扎左前降支建立雄性SD大鼠心肌梗死模型。术前5天随机分成假手术组(n=6),心肌梗死模型组(n=8),肥大细胞稳定剂色甘酸钠治疗组(n=7)。术前3天及术后2周和4周行心脏超声检测心功能。术后4周称取左心室、右心室湿重/体重,HE染色观察病理组织学变化,甲苯胺蓝法检测肥大细胞密度。结果心肌梗死后第2周,与假手术组相比,模型组和治疗组左心室射血分数(LVEF)明显下降(P<0.01)。虽然模型组和治疗组心脏扩大,但三组之间差异无显著性。心肌梗死后第4周,与假手术组相比,模型组和治疗组左心室舒张期末容积(EDV)明显增大(P<0.05)。与模型组相比,治疗组EDV差异无显著性(P>0.05),但LVEF明显增加(P<0.01),左心室肥厚指数下降(P<0.05),心外膜(主要是梗死区)肥大细胞密度明显下降(P<0.01)。且肥大细胞密度与LVEF呈负相关(P<0.01),与左心室肥厚指数呈正相关(P<0.05)。结论肥大细胞直接参与了心肌梗死后的心室重构。肥大细胞脱颗粒的长期抑制明显提高心脏的心搏量,减轻左心室心肌肥厚,进而改善心功能。

The Effects of Mast Cell Stabilizing Compound on Adverse Ventricular Remodeling of Post-Myocardial Infarction in SD Rats

AimTo clarify the effects of the cardiac mast cells on cardiac function after myocardial infarction(MI),and to study the relationship between mast cells and ventricular remodeling after MI in SD rats.MethodsMI model was established in male Sprague-Dawley(SD) rats by ligation of left anterior descending coronary artery.The rats were randomly divided into three groups before 5 days of ligation:sham-operated group(n=6),MI model group(n=8) and mast cell stabilizer cromolyn sodium treatment group(n=7).Before 3 days,after 2 and 4 weeks of ligation,the cardiac function was assessed by Echocardiography.After 4 weeks of treatment,the ratio of left or right ventricular weight and body weight were measured,the change of histopathological were observed,and the density of mast cells were measured.ResultsAs compared with sham-operated group,left ventricular ejection fraction(EF) in MI model group and treatment group was markedly decreased(P<0.01)after 2 weeks of treatment.Although the enlargement of the heart has been going in model group and treatment group,there is no significant difference among these three groups.After 4 weeks of the treatment,the Left ventricular end-diastolic volume(EDV) was significantly increased in model group and treatment group more than in sham-operated group(P<0.05).Compared with MI model group,cromolyn sodium increased EF but not EDV,and decreased left ventricular index(P<0.05) and mast cells density(P<0.01) in left ventricular subepicardial layers of infarted region.The number of mast cells in subepicardial layers had negative correlation with EF,but was positively correlated with left ventricular index.Conclusion Mast cells was directly involved in ventricular remodeling after MI.The long-term mast cell degranulation inhibition can significantly improve the heart’s stroke volume and reduce left ventricular hypertrophy,thereby improving cardiac function.