PNU282987对异丙肾上腺素所致小鼠心脏重塑的保护作用

目的通过建立异丙肾上腺素所致小鼠心脏重塑模型,观察PNU282987保护心脏的作用。方法连续7 d皮下注射异丙肾上腺素(ISO),诱导小鼠心脏重塑模型,同时腹腔给予PNU282987,检测小鼠心脏重量指数、血清乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性,观察心肌病理形态学的改变;检测心肌组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,通过Western blot测定诱导型一氧化氮合酶(iNOS)的表达。结果与正常对照组相比,异丙肾上腺素组心脏重量指数增加,血清LDH和CK水平显著升高,心肌SOD活性下降,MDA含量增加,心肌组织中iNOS蛋白表达增加;与模型组比较,PNU282987可显著降低心脏重量指数、血清LDH和CK水平,增加心肌SOD活性,降低心肌MDA含量,下调iNOS表达。结论 PNU282987可能通过清除氧自由基,降低iNOS的表达,保护异丙肾上腺素导致的小鼠心脏重塑。

Protective effect of PNU282987 on isoproterenol-induced cardiac remodeling in mice

Objective To establish the mice cardiac remodeling model in mice and observe the protective effect of PNU282987. Methods Cardic remodeling model of mice was induced by subcutaneous injection of isoproter-enol for 7 d,then the mices were intraperitoneally injected PNU282987. The heart weight index,serum lactate dehydro-genase ( LDH) and creatine kinase ( CK) activity were measured and the myocardical tissue morphology changes were observed. The content of superoxide dismutase ( SOD) and malondialdehyde ( MDA) in myocardial tissue was meas-ured,and the expression of induced nitric oxide synthase ( iNOS) was detected by using Western blot method. Results Compared with control group,the heart weight index,levels of serum LDH and CK,the content of MDA and the iN-OS protein expression in myocardial tissue in ISO group were increased,and the activity of SOD was reduced. Com-pared with model group,PNU282987 could significantly decrease the cardiac weight index,serum LDH and CK levels and the content of myocardial MDA,and increase myocardial SOD activity,while the expression of iNOS was down-regulated. Conclusion PNU282987 can down-regulate the expression of iNOS by clearing the oxidative stress, and protect the cardiac remodeling induced by isoprenaline in mice.