NF-κB在多柔比星所致大鼠心肌损伤中的作用及褪黑素的治疗作用

目的探讨NF-κB在多柔比星(Dox)心肌病中的作用及褪黑素(MT)的干预作用。方法30只雄性SD大鼠随机分为正常对照组、Dox模型组、Dox+MT组。免疫组织化学法检测NF-κB的活性,分光光密度法检测心肌组织中一氧化氮(NO)含量和诱导型一氧化氮合酶(iNOS)活性,TUNEL法检测心肌细胞凋亡。结果与正常对照组相比,NF-κB在Dox模型组显著活化,MT可抑制NF-κB的激活(P<0.05);与正常对照组相比,Dox组NO含量、iNOS活性和心肌细胞凋亡率显著升高(P<0.05),MT干预后均显著降低。结论NF-κB参与心肌氧化应激损伤,促进心肌细胞凋亡。MT可抑制NF-κB活化,减少自由基的生成,抑制心肌细胞凋亡,对Dox心肌病具有保护作用。

Effects of NF-kappa B on doxorubicin induced myocardium injury and melatonin treatment in rats

OBJECTIVE To investigate the effect of NF-κB on cardiomyopathy induced by doxorubicin(Dox) in rats and the effect of melatonin(MT). METHODS Thirty male Sprague-Dawley rats were randomly divided into 3 groups: normal control group; Dox model group; Dox+MT group. The content of nitric oxide (NO) and the activity of inducible nitric oxide synthase (iNOS) in cardiac tissues were examined by spectrophotography method; the activity of NF-κB in myocardial cell was observed by immunohistochemistry method; the apoptosis information of myocardial cell was detected by TUNEL method. RESULTS There was significant difference in activity of NF-κB between normal control and the Dox model group. MT could inhibit the activation of NF-κB(P＜0.05). There was significant difference in the content of NO and the activity of iNOS between normal control and Dox model group, MT could decrease content of NO and the activity of iNOS(P＜0.05); apoptotic rate in Dox model group was significantly increased compared with that in normal control group, MT could significantly decrease myocardial cell apoptosis (P＜0.05). CONCLUSION The activation of NF-κB plays an important role in cardiomyopathy induced by Dox, NF-κB seems to increase the activity of iNOS, and then significantly increase the content of NO in cardiac muscle; NF-κB possibly enhances myocardial cell apoptosis in cardiomyopathy induced by Dox. MT may inhibit the activation of NF-κB, and prevent excessive oxidative stress and suppress myocardial cell apoptosis, MT has protective effect against cardiomyopathy induced by Dox.