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阿托伐他汀对大鼠心肌缺血再灌注损伤的影响
余慧,秦永文*
0
(第二军医大学长海医院心血管内科,上海 200433
*通信作者)
摘要:
目的 建立大鼠心肌缺血-再灌注损伤模型,观察阿托伐他汀预处理对心肌缺血再灌注损伤的保护作用,并探讨其可能的作用机制。方法 将36只健康雄性SD大鼠随机分为假手术(S)组、缺血再灌注(I/R)组和阿托伐他汀干预(AT+I/R)组,每组12只。采用冠状动脉左前降支结扎法制备大鼠心肌缺血再灌注损伤模型。通过Evans蓝和四氮唑(TTC)染色评估各组大鼠心肌梗死面积;采用放射免疫法测定大鼠缺血未梗死区心肌组织中肿瘤坏死因子α(TNF-α)、丙二醛(MDA)、髓过氧化物酶(MPO)含量及总超氧化物歧化酶(TSOD)活性;采用比色法测定一氧化氮(NO)含量及总一氧化氮合酶(NOS)、诱导型NOS(iNOS)活性。结果 AT+I/R组心肌梗死区与缺血区(缺血未梗死区+梗死区)面积比值低于I/R组\[(29.4±8.4)% vs (57.7±6.5)%,P<0.001\];AT+I/R组梗死面积与左室面积的比值也低于I/R组\[(15.9±5.6)% vs (29.0±8.9)%,P<0.05\]。AT+I/R组及I/R组左室非梗死区域心肌TNF-α、MDA、MPO、NO含量及NOS、iNOS活性均高于S组(P<0.05),而TSOD活性则低于S组(P<0.05);与I/R组比较,AT+I/R组心肌TNF-α、MDA、MPO、NO含量及NOS、iNOS活性均降低(P<0.05),TSOD含量升高(P<0.05)。结论 阿托伐他汀对缺血再灌注损伤心肌具有保护作用,机制可能与其降低炎性反应、激活抗氧化反应、提高机体清除氧自由基能力有关,且iNOS在其中的作用值得重视。
关键词:  阿托伐他汀  再灌注损伤  肿瘤坏死因子α  一氧化氮合酶
DOI:10.3724/SP.J.1008.2012.001070
投稿时间:2012-06-13修订日期:2012-07-25
基金项目:
Protective effect of atorvastatin against myocardial ischemia-reperfusion injury in rats
YU Hui,QIN Yong-wen*
(Department of the Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author.)
Abstract:
ObjectiveTo observe the protective effect of atorvastatin against myocardial ischemia-reperfusion injury in rats and to discuss the possible mechanism. MethodsThirty-six healthy male Sprague-Dawley rats were evenly randomized into three groups: sham-operated (S) group, ischemia-reperfusion (I/R) group, and atorvastatin pretreatment (AT+I/R) group. The myocardial ischemia-reperfusion model was established by ligating the left anterior descending of coronary artery. The infarcted area was evaluated by Evans blue and triphenyltetrazolium chloride (TTC) staining. The contents of tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), and myeloperoxidase (MPO) and total superoxide dismutase(TSOD) activity in the non-infarcted myocardial tissues were measured by radioimmunoassay; the levels of nitric oxide (NO) and the activities of nitric oxide synthase (NOS) and inducible NOS(iNOS) were detected by colorimetric method. ResultsThe ratio of the infarcted area to the ischemia area (ischemia but non-infarcted area+infarcted area) and the ratio of the infarcted area to the left ventricular area in group AT+I/R were both significantly lower than those in group I/R ( \[29.4±8.4)% vs
Key words:  Atorvastatin  Ischemia-reperfusion injury  NOS  TNF-α  oxygen radicals