地塞米松诱导金属硫蛋白表达对大鼠缺血／再灌注损伤心肌的保护作用研究  

Protective effects of metallothionein induced by dexamethasone against ischemia/reperfusion injury of myocardium of isolated rat heart

作　　者：庄梅[1] 方颖[1] 吴立荣[1] 雷大卫[1] 

机构地区：[1]贵阳医学院附属医院心内科, 贵州550004

出　　处：《中国危重病急救医学》2008年第4期223-226,共4页Chinese Critical Care Medicine

基　　金：贵州省科技基金资助项目（J20072099）

摘　　要：目的探讨地塞米松诱导金属硫蛋白（MT）表达对大鼠缺血／再灌注（I／R）损伤心肌的延迟保护作用。方法将32只SD大鼠随机分成地塞米松组和对照组，分别予腹腔注射地塞米松和蒸馏水预处理。预处理24h后构建Langendorff离体心脏I／R动物模型，缺血30min后再灌注60rain。用蛋白质免疫印迹法（Western blotting）检测MT表达；动态观测缺血前及再灌注期间血流动力学指标[左心室发展压（LVDP）、左室内压上升和下降最大速率（±dp／dtmax）、冠状动脉循环流出量（CF）]、心律失常的变化；测定心肌梗死面积、冠状动脉流出液肌酸激酶同工酶（CK—MB）漏出率、心肌丙二醛（MDA）、总超氧化物歧化酶（T—sOD）、铜锌-SOD（CuZn—SOD）、过氧化氢酶（cAT）、谷胱甘肽过氧化酶（GSH—Px）水平及心肌细胞膜Na＋-K＋-ATP酶、Ca22＋-Mg2＋-ATP酶活性。结果与对照组比较，地塞米松组MT的表达水平显著增加（3．085±1．065比1．028±0．016，P〈0．05）；再灌注期间LVDP、±dp／dtmax及CF均得到明显改善（P均〈0．05）；再灌注性室性心律失常评分明显减少[（2．00±1．41）分比（6．63±4．24）分，P〈0．053；心肌梗死面积明显缩小[（28．38±11．22）％比（47．39±8．30）％，P〈0．01]；冠状动脉流出液CK—MB的漏出率明显降低[（8．69±4．16）U／g比（18．15±5．59）U／g，Pdo．01]；心肌组织MDA含量降低（P〈o．05），T—sOD、CuZn—SOD、CAT、GSH—Px均明显升高（P〈0．05或P〈0．01）；心肌细胞膜的Na＋-K＋-ATP酶、Ca2＋Mg2＋-ATP酶活性增加（P〈0．01和P〈O．05）。结论地塞米松可能通过上调MT的表达，对大鼠I／R损伤心肌起到延迟保护作用。Objective To investigate the protective effects of metallothionein （MT） induced by dexamethasone （DEX） against ischemia/reperfusion （I/R） injury of myocardium of isolated rat heart. Methods Thirty-two Sprague-Dawley（SD） rats were divided randomly into the DEX and control groups. In the former group, the rats were pretreated with DEX, and in latter group distilled water was given before their hearts were isolated for Langendorff perfusion and I/R. MT was assessed by Western blotting. The left ventricular developed pressure （LVDP）, maximal change rate of intraventricular pressure rise/down （±dp/dt max）, coronary artery flow （CF） and reperfusion arrhythmias were observed dynamically before ischemia and during 60-minute reperfusion following 30-minute ischemia, The hearts were perfused with triphenyltetrazolium （TTC） after 60-minute reperfusion. The myocardial infarct size was measured with Adobe Photoshop. The levels of MB isoenzyme of creatine kinase （CK-MB）, malonaldehyde （MDA）, total superoxide dismutase （T-SOD）, CuZn-SOD, catalase （CAT）, glutathione peroxidase （GSH-Px） and the activities of Na＋-K＋-ATPase, Ca2＋-Mg2＋-ATPase were detected. Results Compared with control group, the expression of MT was significantly increased （3. 085±1. 065 vs. 1. 028±0. 016, P〈0.05）, the LVDP, ±dp/dt max and CF were greatly improved （all P〈0. 05）, the accumulated point of ventricular arrhythmia and the infarct size were significantly reduced in DEX group [（2. 00±1.41） scores vs. （6.63±4.24） scores and （28.38± 11.22）% vs. （47.39 ± 8.30）%, respectively, both P〈0.01]. The level of CK-MB was significantly lowered in the DEX group compared with control group [（8.69±4.16）U/g vs. （18.15±5.59） U/g, P〈0.01], and myocardium MDA content was decreased （P〈0. 05）. Moreover, the levels of T-SOD, CuZn-SOD, CAT, GSH-Px, and the activites of Na＋-K＋-ATPase and Ca2＋-Mg2＋-ATPase were significantly increased （P〈0. 05 or/and P〈

关 键 词：地塞米松 金属硫蛋白 缺血/再灌注损伤 心肌 心肌保护 

分 类 号：R96[医药卫生—药理学]