地塞米松对大鼠心肌缺血再灌注后细胞凋亡及金属硫蛋白表达的影响  

Effects of dexamethasone on cardiomyocyte apoptosis and expression of metallothionein in rat hearts following ischemia-reperfusion

作　　者：庄梅[1] 方颖[1] 吴立荣[1] 雷大卫[2] 

机构地区：[1]贵阳医学院附属医院心内科,贵阳550004 [2]贵阳医学院生化教研室

出　　处：《中华老年心脑血管病杂志》2008年第7期533-536,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：贵州省科学技术基金[黔科合J字(2007)2099号]

摘　　要：目的观察地塞米松预处理对大鼠心肌缺血再灌注损伤的影响并探讨其作用机制。方法32只SD大鼠随机分成地塞米松组(16只)和对照组(16只),分别给予地塞米松(0.8mg/kg)和蒸馏水腹腔注射。预处理24h后,构建体外心脏缺血再灌注动物模型,动态观测缺血前期及再灌注期左心室发展压(LVDP)、左心室压力最大上升和下降速率(±dp/dtmax)、冠状动脉流出量(CF);测定冠状动脉流出液肌酸激酶同工酶(CK-MB)的漏出率;TUNEL法检测心肌细胞凋亡;Westernblot法检测金属硫蛋白(MT)、Bcl-2及Bcl-xl蛋白的表达;免疫组织化学法测定半胱天冬酶-3(caspase-3)的水平。结果与对照组比较,地塞米松组大鼠再灌注期LVDP、±dp/dtmax及CF得到改善(P<0.05);CK-MB的漏出率明显降低[(8.69±4.16)U/gvs(18.15±5.59)U/g,P<0.01];心肌细胞凋亡指数(10.18±1.99)%vs(14.66±2.97)%和caspase-3水平明显减少[(18.66±5.15)%vs(27.93±6.23)%,P<0.01],Bcl-xl(4.74±0.66)vs(1.69±0.73)和MT的表达明显增加[(3.09±1.07)vs(1.03±0.02),P<0.05],Bcl-2无明显变化(P>0.05)。结论地塞米松预处理对大鼠缺血再灌注的心肌具有保护作用,上调MT表达及抑制细胞凋亡可能是其机制之一。Objective To explore the effects of dexamethasone（DEX） pretreatinent on myocardial ischemia-reperfusion injury（MIRI） in rats and its mechanism. Methods Thirty-two SpragueDawley rats were divided randomly into the DEX group and control （CON） group. The rats had been pretreated with DEX or distilled water 24 hours before their hearts were isolated for Langendorff perfusion and for ischemia-reperfusion. The left ventricular functions （LVDP, ±dp/dtmax）, coronary artery flow （CF） were observed before ischemia and during 60-minute reperfusion following 30-minute ischemia. The levels of CK-MB in the coronary artery flow were measured. Apoptosis was measured by TUNEL staining method. Expression of metallothionein （MT）, Bcl-2 and Bcl-xl protein was assessed by means of Western blot. Caspase-3 was examined by immunohistochemistry. Results Compared with control group, the LVDP, ±dp/dtmax and CF were greatly improved （P 〈0.05）;the apoptotic index, the levels of CK-MB and caspase-3 were significantly decreased （P 〈0. 01） and the expression of Bcl-xl and MT was significantly increased in DEX group （P 〈0.05）. Conclusions DEX has protective effect against MIRI in rats. The mechanism might be the overexpression of MT and the inhibition of cardiomyocte apoptosis.

关 键 词：心肌缺血 地塞米松 细胞凋亡 金属硫蛋白 

分 类 号：R541[医药卫生—心血管疾病]