丹参酮ⅡA对柔红霉素致大鼠心肌损伤的保护作用及其机制  

Protective effect and its mechanism of TanshinoneⅡA on daunorubicin-induced cardiomyocyte injury in rats

作　　者：高雪可 王叨[1] 张靖宇[1] 秦好奇 刘玉峰[1] 

机构地区：[1]郑州大学第一附属医院儿科.河南省儿童血液与肿瘤疾病诊疗中心.郑州大学儿童血液肿瘤研究所,河南郑州450052

出　　处：《中华肿瘤防治杂志》2015年第23期1797-1802,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金重点项目(30930038);国家自然科学基金(81302292)

摘　　要：目的研究表明,丹参酮ⅡA具有抗氧化和抗肿瘤的作用。本研究探讨丹参酮ⅡA(TanshinoneⅡA,TanⅡA)对柔红霉素(daunorubicin,DNR)所致大鼠心脏毒性的预防和减轻作用及机制。方法将50只4周龄健康的雄性SD大鼠按随机数字表法分为空白对照组、DNR组、TanⅡA低剂量组、TanⅡA中剂量组和TanⅡA高剂量组5组。观测其心电活动、左心室射血分数(left ventricular ejection fraction,EF)及左心室短轴缩短指数(left ventricular fractional shortening,FS)的变化;测定各组DNR不同累积量上心肌酶的变化;测定心肌组织活性氧(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)含量的变化;制备常规病理切片,光镜观察心肌细胞的形态和结构变化,Billingham法评价心肌损伤程度。结果 TanⅡA低剂量组60%(6/10)的大鼠出现宽大畸形磁共振血管造影(magnetic resonance angiography,QRS)波;TanⅡA中剂量组30%(3/10)的大鼠出现ST段压低;TanⅡA高剂量组大鼠10%(1/10)的大鼠出现ST段压低,空白对照组未见明显异常。单因素方差分析结果显示,TanⅡA低、中、高组的EF(F=21.45,P<0.01)、FS(F=27.13,P<0.01)均明显高于DNR对照组,且TanⅡA低、中、高组的EF、FS随着TanⅡA剂量增加呈升高趋势。在DNR各累积量上,TanⅡA低、中、高组血清LDH、CK-MB和TNT-HS浓度均显著低于DNR组,以TanⅡA中、高剂量组明显。TanⅡA低、中、高剂量组大鼠心肌组织的ROS(F=21.68,P<0.01)、MDA(F=24.55,P<0.01)均明显低于DNR组,SOD的含量明显高于DNR组(F=22.76,P<0.01),其中TanⅡA中、高剂量组较DNR组变化明显。Billingham法评分结果显示,TanⅡA低、中、高剂量组心肌组织病理积分均显著低于DNR组(F=28.62,P<0.01),以TanⅡA中、高剂量组明显。结论 TanⅡA具有抑制和减轻DNR所致的心肌组织的自由基形成、脂质过氧化等作用,具有保护心肌的作用。OBJECTIVE As researches have shown that Tanshinone Ⅱ A（Tan Ⅱ A） has the effect of Tan Ⅱ A and anti-tumor, we have done this work to study the protective effect and inherent mechanism of Tan Ⅱ A on injured Cardio- myocytes caused by soft erythromycin （DNR）. METHODS Using the table of random numbers, fifty healthy male SD rats, which are all four-week-old, were randomly divided into five groups： blank control group, DNR group, TanⅡ A Ⅰgroup with low dose, TanⅡA Ⅰ group with medium dose, TanⅡ A Ⅰ group with high dose. The detailed procedures are as follow： First, Observing the changes in cardiac electrical activity, left ventricular ejection fraction （LVEF） and the de- flator of left ventricular short axis. Second, measuring the effect of different accumulation of DNR on the changes in myo- cardial enzyme. Third, measuring the changes in the content of cardiac muscle tissue＇s reactive oxygen species（ROS）,malondialdehyde（MDA） and superoxide dismutase（SOD）. Fourth, preparing the routine pathological sections and ob- serving the changes in the shape and structure of myocardial cell using light microscope. And evaluating the damage de- gree of myocardium with the Billingham method. RESULTS Compared with the blank control group, the abnormal rate of rats＇ ECG in the low, medium and high dose of TanⅡ A was 30, 10 and zero percent, respectively. Processed with single factor analysis of variance, the results showed that, compared with group of DNR, both EF（F= 21.45 ,P〈0. 01） and FS （F=27.13,P〈0.01） of the low, medium and high groups of Tan were significantly higher. In addition, EF and FS both showed an uptrend along with the increasing dose of Tan Ⅱ A. As for the DNR accumulation, the serum LDH, CK-MB and TNT-HS in each group（i, e. , low, medium, high） of Tan Ⅱ A were significantly lower than those of DNR group, which were especially obvious in medium and high dose of Tan Ⅱ A group. For the ROS（F= 21.68,P〈0.01） and MDA（F= 24.55, P〈0.01）

关 键 词：丹参酮ⅡA 柔红霉素 心肌损伤 心脏标志物 抗氧化指标 

分 类 号：R285.5[医药卫生—中药学]