骨形态发生蛋白7通过调节GSK-3β活性对心肌梗死后大鼠心肌纤维化的影响  

Effect of Bone Morphogenetic Protein 7 on Myocardial Fibrosis in Rats with Myocardial Infarction through Regulation the Activity of GSK-3β

作　　者：余平 梁鹏[1] 庞诗锋 袁文健 黄巧娟[1] YU Ping;LIANG Peng;PANG Shi-feng;YUAN Wen-jian;HUANG Qiao-juan(Department of Cardiology,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530007)

机构地区：[1]广西医科大学第二附属医院,530007

出　　处：《岭南急诊医学杂志》2021年第1期8-10,51,共4页Lingnan Journal of Emergency Medicine

基　　金：广西医疗卫生适宜技术开发与推广项目(S201414-05)。

摘　　要：目的:探讨外源性骨形态发生蛋白7(Bone morphogenetic protein 7,BMP7)对心肌梗死大鼠心肌纤维化的作用及其对磷酸化的糖原合成酶激酶-3β(p-GSK-3β)和转化生长因子-β1(TGF-β1)蛋白表达的影响。方法:结扎大鼠左冠脉前降支制备心肌梗死模型,随机分为心肌梗死+BMP7组(MI+BMP7组)和心肌梗死组(MI组),每组8只,分别给予BMP7(35μg/kg)或等量生理盐水,每周1次,连续4周。另选6只作为假手术组(Sham组)行相同手术操作而不结扎左前降支。在手术4周后,行苏木素-伊红(HE)染色观察心肌组织病理改变;Masson染色观察心肌纤维化情况;再经蛋白免疫印迹(WB)检测p-GSK-3β和TGF-β1蛋白表达量。结果:与Sham组相比,MI组心肌纤维排列紊乱,可见大量的胶原纤维沉积(P<0.05),p-GSK-3β及TGF-β1的蛋白表达水平明显上调(均P<0.05),而MI+BMP7组与MI组相比,大鼠心肌组织可见胶原纤维沉积减少(P<0.05),p-GSK-3β及TGF-β1的蛋白表达水平明显下调(均P<0.05)。结论:BMP7可有效抑制MI诱导的大鼠心肌纤维化,其机制可能是通过调控GSK-3β活性,抑制TGF-β1/Smads信号传导通路有关。Objective:To investigate the effect of bone morphogenetic protein 7(BMP7)onmyocardial fibrosis in ratswith myocardial infarction and its effect on p-GSK-3βand TGF-β1 protein expression.Methods:The model of myocardial infarction was established by applying ligation of left anterior descending coronary artery.Rats were randomly divided into two groups:MI+BMP7 group(treated by BMP7 with the dose of 35μg·kg-1,once a week for 4 weeks,n=8)andMI group(treated by equal amount of normal saline,once a week for 4 weeks,n=8).In addition,we randomly selected 6 rats as Sham group and only operated without ligation of left anterior descending coronary artery.Then perform Hematoxylin-eosin(HE)staining and Masson staining after surgical procedures 4 weeks,and the expressions of p-GSK-3βand TGF-β1 in myocardial tissue were detected by Western blot.Results:Compared with the sham group,the cardiac fibers in MI group were disordered and collagen fibers were significantly deposited in the myocardial tissue(P<0.05),the expressions of p-GSK-3βand TGF-β1 increased obviously(all P<0.05).However,relative to the MI group,the MI+BMP7 group decreased collagen fibers deposition(P<0.05),reduced expression of p-GSK-3βand TGF-β1(all P<0.05).Conclusion:BMP7 exerts a protective effect on on myocardial fibrosis in rats.Its mechanism may be related toregulation of GSK-3βactivity and inhibition of TGF-β1/Smad3 signaling pathway.

关 键 词：心肌梗死 心肌纤维化 骨形态发生蛋白7(BMP7) GSK-3Β TGF-β1/Smads信号通路 

分 类 号：R542.22[医药卫生—心血管疾病]