目的探讨低分子肝素(LMWH)对大鼠心肌肥厚和纤维化的影响及作用机制。方法异丙肾上腺素(BO)皮下注射致大鼠心肌肥厚纤维化,并观察经LMWH(200U·kg^-1·d^-1)治疗10d后,对大鼠的心脏质量指数、组织形态、血清中一氧化氮(NO)、心肌组织中胶原水平、钙调神经磷酸酶(CaN)活性的影响。结果与对照组比较。损伤组心脏质量指数增加(P〈0.01),出现纤维化病变,心肌中的CaN活性增高(P〈0.01),胶原水平增加(P〈0.01),血清中NO水平减少(P〈0.01);而LMWH保护组与损伤组相比,心肌肥厚和纤维化病变减轻。心肌中的胶原水平减少(P〈0.01),CaN活性降低(P〈0.01),血清中的NO水平显著增高(P〈0.01)。结论LMWH有良好的减轻心肌肥厚和抗心脏纤维化作用,该作用可能与其抑制CaN活性、减少胶原沉积和增加NO水平有关。
Objective To study the effect of low molecular weight heparin (LMWH) on cardiac hypertxophy and fibrosis induced by isoproterenol (ISO) in rats and its mechanism. Methods Cardiac hypertrophy and fibrosis in rats were induced by subcutaneous administration of ISO. LMWH (200 U ·kg^-1 ·d^-1) was administered by subcutaneous injection to treat the rats. The morphological changes and heart mass index, the content of nitric oxide (NO) in serum, the activity of calcineurin (CAN), the content of collagen in the heart were determined after 10 days of treatment. Results The results showed that significant cardiac hypertrophy and fibrosis in rats were induced by ISO on the 10th day. Heart mass index,the activity of CaN and the content of collagen in the heart were increased (P 〈 0.01 ),the content of NO in serum was decreased (P 〈 0.01 ),but all these changes were reversed in LMWH group,with decreased weight of heart and activity of CaN and less content of collagen in the heart (P 〈 0.01 ) and increased content of NO in serum (P 〈 0.01 ). Conclusions LMWH can alleviate the cardiac hypertrophy and fibrosis induced by ISO in rats.