糖皮质激素预处理对兔心肌缺血再灌注损伤的保护作用
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糖皮质激素预处理对兔心肌缺血再灌注损伤
的保护作用
作者:王升儒,成少利,国荣,
刘健,李玲,王明永,许洁,芮俊,钱立雄,高珂
【摘要】目的探讨糖皮质激素对心肌缺血再灌注损伤的保护作用。
方法将18只家兔应用冠状动脉左前降支结扎术造成心肌缺血模型,随机分成3组:心肌缺血再灌注损伤模型组(模型组)、糖皮质激素一次大剂量保护组(大剂量组)以及糖皮质激素多次小剂量保护组(小剂量组),每组6只。
应用BL420生物信号采集系统观察记录心电图ST段改变,分别在缺血前、缺血15min以及再灌注30min 取血测定血浆丙二醛(MDA)浓度;缺血区心肌标本制作冰冻切片,行组织化学染色,观察缺血区琥珀酸脱氢酶活性变化。
结果糖皮质激素的大、小剂量保护组再灌注过程中ST段恢复的时间较短,快于模型组;大剂量组血清MDA水平低于小剂量组(P<0.05),且两组均低于模型组(P<0.01);大剂量组缺血心肌琥珀酸脱氢酶活性高于小剂量组,且两组均明显高于模型组。
结论糖皮质激素对心肌缺血再灌注损伤可以起到有效的保护作用,一次大剂量的治疗保护效果要好于多次小剂量。
【关键词】糖皮质激素心肌缺血再灌注损伤家
ABSTRACT: Objective To study the protective effect of glucocorticoid preconditioning on the myocardial ischemic and reperfused hearts. Methods Totally 18 rabbits were randomly
divided into three groups: myocardial ischemia reperfusion model (model), high dose glucocorticoid given by one time group (high dose group) and low dose glucocorticoid given by several times group (low dose group), with six rabbits in each group. Myocardial ischemia was induced by left anterior descending coronary artery ligation. ST segments were recorded by the BL420 biological signal acquisition system. Plasma malondial dehyde (MDA) was examined before ischemia, at 15min after ischemia and 30min after reperfusion; ischemic heart muscles were prepared with cryotomy and stained histochemically. Succinic dehydrogenase activity was observed in the ischemic region. Results There was shorter time of ST segment recovery in the high dose group and the low dose group than that in the model group. Serum level of MDA in the high dose group was lower than in the low dose group (P<0.05), and both were also lower than that in the model group (P<0.01). The succinate dehydrogenase activity in the high dose group was significantly stronger than in the low dose group, and both were significantly stronger than that in the model. Conclusion Glucocorticoid plays an effectively protective role in myocardial ischemia reperfusion injury. The protective effect of high dose is better than low dose therapy.
KEY WORDS: glucocorticoid; cardiac muscle; ischemica reperfusion injury; rabbit
研究表明再灌注损伤的主要机制是钙超载、自由基损伤及微循环障碍。
近年来已有多项研究证实,中性粒细胞等产生的自由基以及炎症因子使细胞膜脂质过氧化在缺血再灌注损伤中起着重要作用,最终导致细胞坏死和凋亡[1]。
糖皮质激素有抑制氧自由基的释放、抗休克、稳定细胞膜的作用[2],其可抑制中性粒细胞的黏附性、趋化性、分泌功能及花生四烯酸的代谢,减少中性粒细胞对组织细胞的损伤[3]。
本研究应用糖皮质激素预处理对家兔心肌缺血再灌注损伤进行保护治疗,以了解糖皮质激素对心肌缺血再灌注损伤的保护作用,为临床减轻心肌缺血再灌注损伤的发生提供实验依据。
1 材料与方法
1.1 实验动物
体重(2.5±0.1)kg的健康家兔18只(雌雄各半),由西安交通大学医学院实验动物中心提供。
1.2 试剂及仪器
地塞米松注射剂(江苏黄海制药有限公司);TBA(硫代巴比妥酸,上海远帆助剂厂);甲醇、四乙氧基丙烷、正丁醇溶液、200mL/L 三氯醋酸(TCA)等均为分析纯制剂。
BL420生物信号采集系统(成都泰盟科技有限公司)。
1.3 心肌缺血模型的制作及分组
家兔在相同条件下饲养3d后随机分为3组(雌雄各半):模型。