金樱子联合氯沙坦对多柔比星心肌毒性的影响

目的:观察金樱子(Rosa Laevigata Michx,RLM)联合氯沙坦(losartan,LOS)对多柔比星(Doxorubicin,DOX)诱导的心肌损伤的影响。方法:SD大鼠随机分为5组:对照组、模型组、RLM组、LOS组及联合组。除对照组仅给予等体积0.9%氯化钠溶液外,其余4组采用DOX分6次腹腔注射,使其累计剂量达15 mg/kg进行造模。RLM和LOS分别按5 g/kg和0.7 mg/kg剂量单独或联合给予灌胃。测量血清中TNF-α、肌酸激酶(creatine kinase,CK-MB)及乳酸脱氢酶(lactate dehydrogenase,LDH)的含量;同时采用比色法测量过氧化氢酶(hydrogen peroxidase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)的活力以及丙二醛(Malondialdehyde,MDA)的含量。结果:与对照组比较,模型组心脏质量指数、血清TNF-α、CK-MB、LDH水平均升高,心肌组织中MDA、NO含量升高,SOD和CAT活性降低(P<0.05)。与模型组比较,给予RLM或/和LOS干预6周后,心脏质量指数、血清TNF-α、CK-MB、LDH水平均下调,心肌组织中MDA、NO含量均降低,SOD和CAT活性均升高(P<0.05),且联合组效应较单独给药组更加明显(P<0.05)。结论:RLM可协同LOS发挥对DOX诱导的心肌毒性的保护作用,其作用可能与其抗氧化和抗炎症特性有关。

Rosa Laevigata Michx Combined Losartan Against Chronic Cardiotoxicity Induced with Doxorubicin in Rats

Objective To investigate the effects of Rosa laevigata michx （RLM） combined losartan （LOS） on cardiotoxicity induced with doxorubicin （DOX） in rats. Methods SD rats were randomly divided into control group, model group, DOX group, RLM group and combined group. The rats in control group were injected by normal saline, while all the other rats were intraperitoneally injected doxorubicin for 6 times till cumulative dose to 15 mg/kg. Losartan and RLM was single or combined adminstrated with dose of 5.0 g/kg and 0.7 mg/kg. The serum levels of TNF-α, creatine kinase （ CK-MB ）, and lactate dehydrogenase（LDH） were determined. The activities of catalase（CAT） and superoxide dismutase（SOD） ,the con- tent of malondialdehyde（MDA） were all detected with colorimetric method. Results Compared with control group, the heart quality index,serum levels of TNF-α,CK-MB and LDH were significantly increased,the contents of MDA and NO in myo- cardium were increased, but the activities of SOD and CAT were decreased in model group （ all P 〈 0.05 ）. Compared with model group, the heart quality index, serum levels of TNF-α, CK-MB, LDH were significantly down-regulated, the contents of MDA and NO in myocardium were decreased, but the activities of SOD and CAT were increased in treatment groups（ all P 〈 0.05 ）. The effects of combined group were significantly superior to the single losartan or RLM group（ P 〈 0.05 ）. Conclu- sion RLM combined losartan could protect myocardium from cardiotoxieity induced with doxorubicin, which may correlate with its anti-oxidant and anti-inflammatory properties.