骨形态发生蛋白7对心梗后心衰大鼠心肌的保护作用研究

Protective Effect of Bone Morphogenetic Protein 7 on Myocardium in Rats with Heart Failure After Myocardial Infarction

关键词:  心肌梗死  心力衰竭  骨形态发生蛋白7  细胞凋亡  核转录因子-κB

Key words:  myocardial infarction  heart failure  Bone Morphogenetic Protein 7  apoptosis  nuclear transcription factor-κB

摘要:

为探讨骨形态发生蛋白7 (Bone Morphogenetic Protein 7,BMP7)对心梗后心衰大鼠心肌的保护作用及机制，本研究采用左前降支结扎法制备心梗后心衰模型，将大鼠随机分为心肌梗死(MI)组和心肌梗死+BMP7(MI+BMP7)组，每组8只。另选6只作为假手术(Sham)组，假手术组不结扎前降支。结扎前降支后第2天，MI+BMP7组给予BMP7 (35 μg·kg^-1),Sham组与MI组给予等体积的生理盐水，每周1次，连续4周。干预结束后，对大鼠心功能、血浆NT-proBNP含量、心肌组织病理改变、心肌细胞凋亡率，以及Bcl-2、Bax、Cleaved caspase-3和p-NF-κB p65蛋白的表达进行测定。结果表明，与Sham组相比，MI组左室射血分数(LVEF)值和左室短轴缩短率(LVFS)值显著降低(P<0.05)，血浆NT-proBNP表达显著增加(P<0.05)，心肌组织出现大量纤维化，伴有炎性细胞浸润，心肌细胞凋亡率显著升高(P<0.05)，Bcl-2蛋白表达显著降低(P<0.05)，Bax、Cleaved caspase-3和p-NF-κB p65蛋白表达显著升高(P<0.05)。与MI组相比，MI+BMP7组LVEF值和LVFS值显著升高(P<0.05)，血浆NT-proBNP表达显著降低(P<0.05)，心肌细胞坏死减少，心肌纤维化及炎症反应减轻，细胞凋亡率降低，Bcl-2蛋白表达显著升高(P<0.05)，Bax、Cleaved caspase-3和p-NF-κB p65蛋白表达显著降低(P<0.05)。综上可知，早期应用外源性BMP7可改善心梗后心衰大鼠的心脏功能，其机制可能与抑制NF-κB p65和Caspase-3的活化，减少心肌细胞凋亡有关。

Abstract:

The protective effect and mechanism of Bone Morphogenetic Protein 7 (BMP7) on heart failure after myocardial infarction in rats are investigated.In this study,the model of heart failure after myocardial infarction was prepared by ligation of the left anterior descending branch.The rats were randomly divided into Myocardial Infarction (MI) group and Myocardial Infarction+BMP7 (MI+BMP7) group,with 8 rats in each group.Another 6 rats were selected as Sham group,and the anterior descending branch was not ligated in the sham operation group.On the 2nd day after ligation of the anterior descending branch,the MI+BMP7 group was given BMP7 (35 μg·kg^-1),and the sham group and the MI group were given the same volume of normal saline once a week for 4 consecutive weeks.After the intervention,the cardiac function,plasma NT-proBNP content,pathological changes of myocardial tissue,cardiomyocyte apoptosis rate,and the expression of Bcl-2,Bax,Cleaved caspase-3 and p-NF-κB p65 protein were measured.The results showed that compared with the Sham group,the Left Ventricular Ejection Fraction(LVEF) value and Left Ventricular Fractional Shortening (LVFS) value of the MI group were significantly decreased (P<0.05),the expression of plasma NT-proBNP was significantly increased (P<0.05),myocardial tissue appeared a large number of fibrosis,accompanied by inflammatory cell infiltration,apoptosis rate was significantly increased (P<0.05),Bcl-2 protein expression was significantly decreased (P<0.05),Bax,Cleaved caspase-3 and p-NF-κB p65 protein expression was significantly increased (P<0.05).Compared with MI group,the LVEF and LVFS in MI+BMP7 group were significantly increased (P<0.05),the expression of plasma NT-proBNP was significantly decreased (P<0.05),myocardial cell necrosis was reduced,myocardial fibrosis and inflammation were alleviated,cardiomyocyte apoptosis rate was decreased,the expression of Bcl-2 protein was significantly increased (P<0.05),and the expression of Bax,Cleaved caspase-3 and p-NF-κB p65 protein was significantly decreased (P<0.05).In summary,early application of exogenous BMP7 can improve cardiac function in rats with heart failure after myocardial infarction,and its mechanism may be related to inhibiting the activation of NF-κB p65 and Caspase-3 and reducing cardiomyocyte apoptosis.