阿托伐他汀干预对大鼠心肌缺血再灌注后GRP78和GADD153表达的影响  

Effects of atorvastatin on the expression of endoplasmic reticulum molecular chaperone GRP78 and GADD153 following myocardial ischemia-reperfusion injury in rats

作　　者：刘忠仁[1] 王若琦[1] 蓝景生[1] 谭志辉[1] 

机构地区：[1]右江民族医学院附属医院心血管内科,广西百色533000

出　　处：《右江医学》2010年第5期517-520,共4页Chinese Youjiang Medical Journal

基　　金：广西青年科学基金资助项目(NO.桂科青0832098)

摘　　要：目的观察阿托伐他汀干预对大鼠心肌缺血再灌注损伤后内质网分子伴侣GRP78（endoplasmic reticulummolecular chaperon）和GADD153（growth arrest and DNA damage-inducible gene 153）表达变化的影响,探讨阿托伐他汀在心肌缺血再灌注损伤后抗凋亡的内质网应激机制。方法将54只SD大鼠随机分为阿托伐他汀干预组24只、模型对照组24只和假手术组6只,制作大鼠心肌再灌注损伤模型。阿托伐他汀干预组和模型对照组再灌注2 h6、h、24 h、48 h分别分为4个亚组,每个亚组动物6只。通过TUNEL检测心肌细胞凋亡,免疫组织化学检测GRP78和GADD153表达变化。结果假手术组大鼠偶可见凋亡细胞,对照组和干预组大鼠缺血再灌注2 h缺血周围区可见少量凋亡细胞,再灌注6 h凋亡细胞有所增多,再灌注24 h凋亡细胞数量达高峰,再灌注48 h凋亡细胞有所减少（P〈0.05或0.01）。相同各时间点比较,干预组大鼠心肌细胞凋亡显著少于对照组（P〈0.05或0.01）。假手术组大鼠心尖部相应区域心肌细胞未见明显GRP78及GADD153阳性表达。对照组和干预组大鼠再灌注2 h后心尖部GRP78表达开始增加,6 h达高峰,24 h时表达水平明显下降（P〈0.01）。在相应时间点,干预组的GRP78蛋白表达水平显著高于对照组（P〈0.01）。对照组和干预组大鼠缺血周围区GADD153从再灌注6 h开始在神经细胞内明显表达,并逐渐增强,于再灌注24~48 h达高峰（P〈0.01）。在相应时间点,干预组的GADD153蛋白表达水平显著低于对照组（P〈0.01）。结论干预心肌缺血再灌注后心肌细胞内质网伴侣GRP78和GADD153的表达可能是阿托伐他汀抑制心肌缺血再灌注损伤后抗凋亡的内质网应激机制之一。Objective To observe effects of atorvastatin on the expression of endoplasmie reticulum molecular chaperone GRP78 and GADD153 following myocardial ischemia-reperfusion injury in rats, and further explore the mechanism of atorvastatin on anti-apoptosis by endoplasmic reticulum stress. Methods Fifty-four Sprague-Dawley rats were randomly divided into 3 groups： sham group（n~ 6）, model group（n~ 24）, and atorvastatin intervention group（n=24）. The expression of GRP78 and GADD153 in rats striatum was detected by immunohistochemistry staining,the myocardial apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling （TUNEL）. Results Contentsmyocardial apoptosis in the intervention group significantly reduced compared with mod- el group at each time point（ P d0.01）. The expression of GRP78 was increased at 2 h following myocardial ischemiareperfusion, and peaked at 6 h,obviously declined at 24 h in both intervention group and model group. However,The GRP78 expression at each time point in intervention group was higher than those in control groups（ P 〈0.05）. While The expression of GADD153 was increased at 6 h following myocardial ischemia-reperfusion,and peaked at 24~48 h in both intervention group and model group. The GADD153 expression at each time point in intervention group was higher than those in control groups（ P 〈0.05 or 0.01）. Conclusion Interfere the expression of endoplasmic reticulum molecular chaperone GRP78 and GADD153 may be one of the mechanisms of the atorvastatin anti-apoptosis following myocardial ischemia-reperfusion.

关 键 词：阿托伐他汀 GRP78 GADD153 细胞凋亡 缺血-再灌注损伤 

分 类 号：R541.4[医药卫生—心血管疾病]