摘要
目的 探讨外源性肝细胞生长因子对心肌梗死后心肌细胞的影响。方法 3 6只新西兰兔随机分为 3组 :假手术组、对照组和干预组。结扎左冠状动脉前降支复制急性心肌梗死模型。干预组静脉注射给予肝细胞生长因子 2mg·kg- 1 ·12h- 1 ,48h后测心功能 ,梗死区 缺血区质量比代表梗死范围。TUNEL法染色检测细胞凋亡 ,确定心肌细胞凋亡指数。Westernblot法测定凋亡蛋白bcl 2、ERK1及pERK1的表达。结果 ①干预组心肌梗死范围显著小于对照组 (P <0 .0 1)左室功能得以改善 ;②干预组心肌细胞凋亡指数显著低于对照组 (P <0 .0 5 ) ;③干预组梗死心肌周围bcl 2表达显著高于对照组 (P <0 .0 5 ) ;④实验组ERK1的表达不明显 ,但pERK1的表达显著升高。结论 外源性肝细胞生长因子能显著减少急性心肌梗死后的梗死范围、抑制心肌细胞凋亡及改善左室功能 ,作用途径可能与促进抗凋亡蛋白bcl 2表达有关。ERK1 2磷酸化可能作为外源性肝细胞生长因子的信号通路参与了心肌保护作用。
Objective To explore the effects of exogenous hepatocyte growth factor (HGF) on cardiomyocytes in acute myocardial infarction (AMI) rabbits. Methods Rabbit model of ligated proximal left anterior descending coronary artery (LAD) was used. Thirty six rabbits were randomly divided into three groups: sham operation (SO), control (CG) and intervention (IG) groups. The animals in sham operation and control groups were intravenously infused with normal saline, but those in the intervention group were intravenously administered with HGF (2 mg·kg -1 ·h -1 ). At 48 h after ligated LAD, the hemodynamic studies were performed in each group, and ischemic area and the infarct size were also measured. Cell apoptosis was detected by TUNEL straining, and the expressions of bcl 2, ERK1 and pERK1 proteins were analyzed by Western blotting. Results ① The infarct size in the intervention group was significantly smaller than that in the control group ( P =0.002), and the left ventricular function was improved. ② The myocardial apoptotic index in the intervention group was significantly lower than that in the control group ( P =0.02). ③ The expression of bcl 2 proteins in the intervention group was significantly higher than that in the control group. Exogenous HGF could promote the expression of bcl 2 proteins. No significant difference in the expression of ERK1 was not found between the groups, but the expression of pERK1 in the intervention group increased significantly as compared with that in the control group. Conclusion Exogenous HGF can decrease infarct area, inhibit cardiomyocyte apoptosis and improve left ventricular function. The mechanism may probably be associated with the promotion of the expression of antiapoptotic bcl 2 proteins. As one of signal transduction pathways, phosphorylation of ERK1 is associated with the HGF cardioprotection.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2004年第14期1255-1257,共3页
Journal of Third Military Medical University
关键词
肝细胞生长因子
ERK
心功能
心肌梗死
凋亡
兔
hepatocyte growth factor
apoptosis
acute myocardial infarction
ERK
rabbit
