白藜芦醇改善阿霉素性心衰的机制研究

Mechanisms of resveratrol improve doxorubicin heart failure

目的:探讨白藜芦醇(resveratrol,RSV)对阿霉素(doxorubicine,Dox)诱导大鼠慢性心衰的影响及其作用机制。方法:取SD雄性大鼠60只,通过使用剂量递增的方法(1,2,3 mg/kg)腹腔注射阿霉素,成功建立慢性心衰模型。将心衰大鼠随机分为地高辛(阳性药)和白藜芦醇组(浓度分别为25.0,12.5,6.25mg/kg),另设空白对照组及模型组。各组均经过灌胃给药(20 ml/kg),给药3周后测定各组大鼠血流动力学参数左室收缩压(LVSP)、左室内压上升及下降最大速率(+dp/dtmax),WST微板法和TBA法检测心脏组织超氧化物岐化酶(SOD)、丙二醛(MDA)及总巯基的含量。Masson染色明确心肌间质胶原纤维增生情况,免疫组织化学方法观察心肌8-羟基脱氧鸟苷的表达。Western免疫印迹检测SIRT1蛋白表达情况。结果:与模型组比较,白藜芦醇25mg/kg浓度时明显改善大鼠心肌间质胶原纤维增生,降低8-羟基脱氧鸟苷大量表达,并且增加大鼠血流动力学LVSP、(+)dp/dtmax参数,增加心肌超氧化物岐化酶、总巯基的含量。蛋白免疫印迹显示白藜芦醇组剂量依赖性明显上调SIRT1蛋白表达。结论:白藜芦醇可减轻阿霉素诱导心衰大鼠的氧化损伤,这种保护可能是通过上调SIRT1来实现的。

Objective： To observe mechanisms and effects of resveratrol （Res） on the heart function of the rats by doxorubicine（Dox）. Methods： By using the method of dose escalation intraperitoneal injection Dox, we have successfully established model of chronic heart failure, sisty rats were randomly divided into Model group, Digaoxin group （4 mg/kg）, Res high, Middle, Low group （ 25,12.5,6.25 mg/kg） and the control group. During 21 days each group were administered orally （20 ml/kg） ,we measured hemodynamic parameters LVSP, ＋ dp/dtmax,The con- tents of superoxide dismutase（ SOD）, malondialdehyde （MDA） and Total thiol （TSH） were detected by hydroxylamine and TBA methods. Masson staining showed myocardial interstitial collagen fiber hyperplasia, Immunohistochemical expression observed cardiac 8-hydroxy-deox- yguanosine, Western immunoblotting to detect the expression of SIRT1 protein. Result： Compared with the model group, RSV group improved significantly between myocardial interstitial collagen fibers, Reduce the large number of 8-hydroxy-deoxyguanosine expression and reduced he- modynamics parameters LVSP and （ ＋ ） dp/dtmax, Increased the content of SOD, TSH （ P 〈 0.05, P 〈 0.01 ）. Western blot displayed a dose- dependent RSV significantly increased the expression of SIRT1 protein （ P 〈 0.05, P 〈 0.01 ）. Conclusion： RSV can reduce Dox-induced oxi- dative damage in rats with heart failure, this protection may be achieved by upregulating SIRT1.