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主动脉缩窄致大鼠左心功能不全对肺血管重构的影响及与BMP7表达的关系
Effects of transverse aortic constriction-induced left ventricular dysfunction on pulmonary vascular remodeling in rats and its relationship with bone morphogenetic protein 7
- 第三军医大学学报 2020年42卷第14期 页码：1385-1391
- 作者机构：
1.400010 重庆，重庆医科大学附属第二医院心血管内科
2.518055 广东 深圳，深圳大学总医院心血管内科
3.400037 重庆，陆军军医大学(第三军医大学)第二附属医院心血管内科
- 作者简介：
[周骐, E-mail: drzhouqi@126.comZHOU Qi, E-mail: drzhouqi@126.com
- 基金信息：广东省基础与应用基础研究基金(2019A1515011421);深圳大学总医院科技助推计划(SUGH2018QD048);深圳市科技计划项目(JCYJ20190808122207499)
DOI：10.16016/j.1000-5404.202002118
中图分类号： R322.12;R363.21;R541收稿：2020-02-18，
修回：2020-05-04，
纸质出版：2020-07-30
- 稿件说明：
移动端阅览
胡骏豪, 武晓静, 顾文竹, 等. 主动脉缩窄致大鼠左心功能不全对肺血管重构的影响及与BMP7表达的关系[J]. 第三军医大学学报, 2020,42(14):1385-1391.
Junhao HU, Xiaojing WU, Wenzhu GU, et al. Effects of transverse aortic constriction-induced left ventricular dysfunction on pulmonary vascular remodeling in rats and its relationship with bone morphogenetic protein 7[J]. Journal of Third Military Medical University, 2020, 42(14): 1385-1391.
胡骏豪, 武晓静, 顾文竹, 等. 主动脉缩窄致大鼠左心功能不全对肺血管重构的影响及与BMP7表达的关系[J]. 第三军医大学学报, 2020,42(14):1385-1391. DOI： 10.16016/j.1000-5404.202002118.
Junhao HU, Xiaojing WU, Wenzhu GU, et al. Effects of transverse aortic constriction-induced left ventricular dysfunction on pulmonary vascular remodeling in rats and its relationship with bone morphogenetic protein 7[J]. Journal of Third Military Medical University, 2020, 42(14): 1385-1391. DOI： 10.16016/j.1000-5404.202002118.
摘要
目的
2
通过大鼠主动脉弓缩窄(transverse aortic constriction，TAC)建立左心功能不全模型，观察对肺血管重构和肺血流动力学的影响及与肺组织骨形成蛋白7(bone morphogenetic protein 7，BMP7)表达的关系。
方法
2
16只健康雄性SD大鼠根据建模分为手术组(TAC组，
n
=8)和假手术组(Sham组，
n
=8)，TAC组行主动脉弓缩窄术；Sham组仅穿丝线不结扎主动脉弓。术后9周时，采用超声心动图检测大鼠左心结构和功能变化，通过心导管术观察肺血流动力学和右心功能的变化，采用HE、Masson染色观察心肌和肺血管变化，采用RT-qPCR、Western blot分别检测肺组织中BMP7 mRNA和蛋白表达。
结果
2
与Sham组相比，术后9周，超声心动图检测发现TAC组大鼠左室后壁和室间隔增厚、左室舒张容积增加(
P
<
0.01)，左室射血分数降低(
P
<
0.01)；血流动力学检测提示TAC组平均肺动脉压升高(
P
<
0.01)，右心室收缩压升高(
P
<
0.01)；病理学观察提示TAC组左室心肌细胞横截面积增大(
P
<
0.01)，心肌纤维化程度增加(
P
<
0.01)，肺小动脉中层增厚程度增加(
P
<
0.01)；RT-qPCR和Western blot检测发现TAC组肺组织中BMP7 mRNA和蛋白表达均减少(
P
<
0.05)。
结论
2
左心重构和左室功能不全引起肺高压和肺血管重构时，除与血流动力学因素直接有关外，可能还与肺组织BMP7表达减少有关，提示心脏对肺的器官间调节可能参与了左心疾病相关肺高压的形成。
Abstract
Objective
2
To study the effects of left ventricular dysfunction induced by transverse aortic constriction (TAC) on pulmonary vascular remodeling and hemodynamics
and the relationship with bone morphogenetic protein 7 (BMP7) expression in the lung tissues of rats.
Methods
2
Sixteen healthy male Sprague-Dawley rats were randomized equally into TAC model group and sham operation group. At the end of 9 weeks after the surgery
cardiac remodeling and the changes of cardiac functions were assessed by cardiac ultrasound. The pulmonary hemodynamic parameters and the right ventricular functions were evaluated by cardiac catheterization. HE and Masson staining was used to observe pulmonary vascular remodeling
left ventricular myocardial cell size and left ventricular myocardial cell fibrosis in the rats. The mRNA and protein levels of BMP7 in the lung tissues of the rats were detected using RT-qPCR and Western blotting.
Results
2
Compared with the sh
am-operated rats
the rats with TAC showed significantly increased left ventricular wall and septal thickness
increased left ventricular end-diastolic volume (
P
<
0.01)
and decreased left ventricular ejection fraction (
P
<
0.01). Hemodynamic analysis showed significant increases of the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) in rats with TAC as compared with the sham-operated rats (
P
<
0.01). Pathological examination revealed that in rats with TAC
the cross-sectional area of the left ventricular cardiomyocytes increased significantly (
P
<
0.01) with obvious myocardial fibrosis (
P
<
0.01) and thickening of the medial layer of the pulmonary arterioles (
P
<
0.01) in comparison with the sham-operated group. The expression of BMP7 was decreased significantly at both the mRNA and protein levels in the pulmonary tissue in TAC group as compared with the sham-operated group (
P
<
0.05).
Conclusion
2
Pulmonary hypertension and pulmonary vascular remodeling caused by left ventricular remodeling and left ventricular dysfunction might be related to decreased pulmonary BMP7 expression in addition to the direct influence by changes in the hemodynamics
suggesting that the organ crosstalk between the heart and the lung might participate in the occurrence of pulmonary hypertension resulting from left heart diseases.
关键词
Keywords
references
WEITSMAN T, WEISZ G, FARKASH R, et al . Pulmonary hypertension with left heart disease: prevalence, temporal shifts in etiologies and outcome[J ] . Am J Med, 2017, 130(11): 1272-1279. DOI: 10.1016/j.amjmed.2017.05.003.
FAYYAZ A U, EDWARDS W D, MALESZEWSKI J J, et al . Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction[J ] . Circulation, 2018, 137(17): 1796-1810. DOI: 10.1161/circulationaha.117.031608.
MERINO D, VILLAR A V, GARCÍA R, et al . BMP-7 attenuates left ventricular remodelling under pressure overload and facilitates reverse remodelling and functional recovery[J ] . Cardiovasc Res, 2016, 110(3): 331-345. DOI: 10.1093/cvr/cvw076.
DIN S, SARATHCHANDRA P, YACOUB M H, et al . Interaction between bone morphogenetic proteins and endothelin-1 in human pulmonary artery smooth muscle[J ] . Vascul Pharmacol, 2009, 51(5/6): 344-349. DOI: 10.1016/j.vph.2009.09.001.
LIU D, WU B X, SUN N, et al . Elevated levels of circulating bone morphogenetic protein 7 predict mortality in pulmonary arterial hypertension[J ] . Chest, 2016, 150(2): 367-373. DOI: 10.1016/j.chest.2016.03.007.
ROSENKRANZ S, GIBBS J S R, WACHTER R, et al . Left ventricular heart failure and pulmonary hypertension[J ] . Eur Heart J, 2016, 37(12): 942-954. DOI: 10.1093/eurheartj/ehv512.
LAM C S, ROGER V L, RODEHEFFER R J, et al . Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study[J ] . J Am Coll Cardiol, 2009, 53(13): 1119-1126. DOI: 10.1016/j.jacc.2008.11.051.
SHAH A M, CLAGGETT B, SWEITZER N K, et al . Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial[J ] . Circ Heart Fail, 2014, 7(5): 740-751. DOI: 10.1161/CIRCHEARTFAILURE.114.001583.
LEUNG C C, MOONDRA V, CATHERWOOD E, et al . Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction[J ] . Am J Cardiol, 2010, 106(2): 284-286. DOI: 10.1016/j.amjcard.2010.02.039.
WANG Y X, QIAN L X, LIU D, et al . Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancerfactor 2a to control embryonic cardiac contractility[J ] . Cardiovasc Res, 2007, 74(2): 290-303.
SUN B, HUO R, SHENG Y, et al . Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy[J ] . Hypertension, 2013, 61(2): 352-360. DOI: 10.1161/HYPERTENSIONAHA.111.00562.
SUN L J, YU J, QI S, et al . Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves cardiac function after myocardial infarction[J ] . J Cell Biochem, 2014, 115(11): 1868-1876. DOI: 10.1002/jcb.24856.
LONG L, ORMISTON M L, YANG X, et al . Selective enhancement of endothelial BMPR-Ⅱ with BMP9 reverses pulmonary arterial hypertension[J ] . Nat Med, 2015, 21(7): 777-785.
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