白藜芦醇保护三氧化二砷引起的心肌毒性的实验研究

The study of protective effect of resveratrol on As_2O_3-induced cardiotoxicity

目的评估白藜芦醇在预防三氧化二砷(Arsenic trioxide,As2O3)引起心肌损伤方面的作用。方法 50只雄性Wistar大鼠随机分为5组:正常对照组(单独给予生理盐水),As2O3对照组(单独给予As2O3),白藜芦醇低剂量组(白藜芦醇5 mg/kg+As2O3)、白藜芦醇中剂量组(白藜芦醇15 mg/kg+As2O3)、白藜芦醇高剂量组(白藜芦醇45 mg/kg+As2O3)。所有治疗均隔1天进行,第6天处死大鼠。用标准肢体Ⅱ导联测定大鼠心电图变化;测定大鼠血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactate dehydrogenasem,LDH)、超氧化物歧化酶(superoxidedismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性以及丙二醛(malondialdehyde,MDA)含量;光镜下观察心肌组织结构变化;四甲基偶氮唑盐比色法(MTT)比色法测定As2O3和白藜芦醇抗肿瘤效应。结果①与正常对照组相比,As2O3对照组大鼠血清CK、LDH活力显著升高,MDA含量升高,SOD及GSH-Px活力下降,具有显著性差异(P<0.05)。②白藜芦醇各剂量(5、15、45 mg/kg)均能减轻As2O3引起的上述改变,与As2O3对照组相比,可降低血清CK、LDH活力及MDA含量,增强血清SOD及GSH-Px活力,以白藜芦醇高剂量组作用最为显著。③光镜下见白藜芦醇可减轻心肌组织结构损伤,白藜芦醇的治疗作用以高剂量组最为显著。④体外研究证实白藜芦醇可增加As2O3的抗肿瘤作用。结论①As2O3引起心脏毒性的发生机制可能与氧自由基及其诱导的脂质过氧化有关。②大剂量白藜芦醇对As2O3所致心脏毒性具有预防作用,其机制可能与其提高机体内抗氧化酶活性及拮抗脂质过氧化有关。

Objective To evaluate the protective effects of resveratrol on As2O3-induced cardiac injury.Methods 50 male Wistar rats were randomly divided into five groups： normal control group（treated with single normal saline）,As2O3 control group（treated with single As2O3）,resveratrol-low dose group（resveratrol 5 mg/kg combined with As2O3）,resveratrol-middle dose group（resveratrol 15 mg/kg combined with As2O3）,and resveratrol-high dose group（resveratrol 45 mg/kg combined with As2O3）.All treatments were given on alternate days,and all rats were sacrificed on the sixth day.The standard limb lead Ⅱ ECG was recorded by an ECG record.Creatine kinase（CK）,lactate dehydrogenase（LDH） and superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px） activities and malondialdehyde（MDA） levels were de termined in serum.Morphological examination was conducted under a light microscope.The anticancer role of resvera trol and/or As2O3 were measured by MTT.Results ①Compared with normal control group,a single dose of As2O3 resulted in significant increase in serum CK,DHL,MDA and decrease in serum SOD and GSH-Px（P〈0.05）.②Obviously,resveratrol attenuated As2O3-induced cardiotoxicity（5,15,45 mg/kg） manifested by normalizing the increase of serum LDH,CK and MDA and the decrease in SOD and GSH-Px（P〈0.05）.③Structural abnormalities in As2O3-treated hearts were prevented by pretreatment with resveratrol.The protective effect of resveratrol-higher dose group was most significant.④A cytotoxic study showed that resveratol could increase the antineoplastic activity of As2O3 to A549 adenocarcinoma cells in vitro.Conclusion ①Oxidative stress and lipid peroxidation may play an important role in As2O3induced heart damage.②Resvertrol attenuates As2O3-induced cardiotoxicity by increasing serum antioxidase activities and decreasing lipid peroxidation.