摘要
目的探讨Ghrelin对急性心肌梗死(AMI)模型大鼠心功能的影响及其可能机制。方法成年雄性SD大鼠18只,结扎冠状动脉前降支建立AMI模型。于建模后第4天,将存活的14只大鼠随机分为模型组(AMI+NS组,n=7)和处理组(AMI+Ghrelin组,n=7),处理组按100μg/kg皮下注射Ghrelin,2次/d,间隔12h,共2周,模型组按100μg/kg皮下注射生理盐水(NS)。另设假手术组(n=8)。2周后,超声心动图(UCG)检测大鼠心功能,ELISA法检测血清LDH、CK-MB含量,HE染色观察心肌组织形态学变化,Western blotting检测内质网应激(ERS)标志物GRP-78、CHOP蛋白表达。结果成功建立AMI大鼠模型。与假手术组比较,UCG提示模型组大鼠心功能明显下降(P<0.05),HE染色可见组织疏松、水肿较明显,血清LDH、CK-MB明显升高(P<0.05),Western blotting检测显示GRP-78、CHOP蛋白表达增加(P<0.05);与模型组比较,处理组心功能明显改善,组织疏松、水肿明显减轻,血清LDH、CK-MB降低(P<0.05),GRP-78、CHOP蛋白表达下降(P<0.05)。结论 Ghrelin可能通过抑制ERS途径改善AMI引起的心肌损伤,从而改善心功能。
Objective To establish the rat model of acute myocardial infarction （AMI）, and to explore the mechanism of ghrelin in improving cardiac function through inhibiting endoplasmic reticulum stress （ERS）. Methods AMI model was repro- duced in 18 adult male Sprague-Dawley rats （220 ＋ 20g） by ligation of the left anterior descending coronary artery. Four days after the reproduction of the model, 14 survived rats with AMI were randomly divided into two groups （7 each）： model group, animals were subcutaneously （sc） injected with normal s aline only; treatment group, animals were given ghrelin （1001zg/kg） twice a day （12h interval） for two weeks. In addition, a sham-operated group was set up （Sham operation＋saline, n=8）. Two weeks later, the cardiac function was examined by echocardiography （UCG）, the morphological changes in myocardial tissue were observed with hematoxy- lin-eosin （HE） staining, the levels of LDH and CK-MB were determined by ELISA, and the expressions of glucose-regulated protein 78 （GRP-78） and C/EBP homologous protein （CHOP） were assessed by Western blotting. Results AMI model was successfully reproduced in SD rats. Compared with the rats in sham group, those in model group showed poor cardiac function （P〈0.05）, HE staining revealed loosening of tissue and edema, ELISA revealed elevation of serum LDH and CK-MB levels （P〈0.05）, and up regu- lation of expressions of GRP-78 and CHOP protein （P〈0.05）. While compared with model group, rats in treatment group showed better cardiac function （P〈0.05）, tissue loosening and edema were alleviated, the levels of serum LDH and CK-MB lowered （P〈0.05）, and inhibition of the expressions of GRP-78 and CHOP protein （P〈0.05）. Conclusion Ghrelin may improve the cardiac function by inhibiting ERS, thus ameliorating the myocardial damage caused by AMI.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2012年第11期1023-1026,共4页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金面上项目(30670870)
重庆市科委自然科学基金(CSTC2012JJA10085)~~
关键词
GHRELIN
心肌梗死
内质网应激
ghrelin
myocardial infarction
endoplasmic reticulum stress
作者简介
【作者简介]蔡敏，硕士研究生。主要从事心力衰竭的基础与临床研究
[通讯作者]刘地川，E-mail：ldc670220@163．com
