Pathological Changes of Heart and Lung Tissues in Rats with Pulmonary Hypertension Induced by Monocrotaline_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YangYongchao , YangDongpeng , YangBo , LinXi , DongWenpeng ,  WangXiaowu

Department of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China;

Corresponding author：

WangXiaowu, Email: xzwk_wxw@hotmail.com

Keywords：

Monocrotaline; Pulmonary arterial hypertension; Animal model

DOI：

10.7507/1671-6205.2015094

Video：

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Objective To observe the pathological changes in heart and lung tissues in rats with pulmonary hypertension induced by monocrotaline. Methods Twenty-four male Sprague-Dawley rats were randomly and equally divided into an experimental group and a control group. The rats in the experimental group were intraperitoneally injected with monocrotaline to induce pulmonary hypertension, and the rats in the control group were treated with saline. All rats were fed for 3 weeks, and the general situation were observed. Then the rats were sacrificed for measurement of mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index [RV/(LV+S)], changes of myocardial cells and lung vascular, calculated density of middle membrane smooth muscle cells (SMC) in medium/small pulmonary arteries accompanied with bronchi and alveoli, media thickness of pulmonary artery (PAMT), the percentage of wall thickness with outer diameter (WT%), the percentage of wall area with total area (WA%), the average diameter of myocardial cells (AD), and myocardial nuclei density (MND). Results Compared with the control group, the condition of rats in the experimental group were getting worse obviously.mPAP and RV/(LV+S) were both increased (both P < 0.05). The observation by light microscope revealed that obvious myocardial hypertrophy and structure disturbances, severe luminal stenosis of medium/small pulmonary arteries, medial thickening, infiltration of inflammatory cell in tissue space, proliferation of unorganized collagen fibers in the experimental group. The observation by electronic microscope showed proliferation of endothelial cell with irregular nuclei, increased organelles and vacuoles in the experimental group. The differences in SMC, PAMT, WT%, WA%, AD, and MND were significant between two groups (all P < 0.05). Conclusions The monocrotaline can induced pulmonary hypertension and right ventricular hypertrophy. The mechanism may be related to severe stenosis or occlusion of the vessel lumen caused by plexiform proliferation of endothelial cells, proliferation of smooth muscle cells and collagen fibers, compensatory hypertrophy and hyperplasia of myocardial cells.

Citation： YangYongchao, YangDongpeng, YangBo, LinXi, DongWenpeng, WangXiaowu. Pathological Changes of Heart and Lung Tissues in Rats with Pulmonary Hypertension Induced by Monocrotaline. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(4): 380-384. doi: 10.7507/1671-6205.2015094 Copy

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7.	陈晓辉, 翁国星, 林群.一种新型的大鼠肺动脉高压模型.中华实验外科杂志, 2005, 22:882.
8.	卢杰, 李梦涛, 王迁, 等.结缔组织疾病相关肺动脉高压动物模型.中华临床免疫和变态反应杂志, 2009, 3:116-121.
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12.	Kerstjens-Frederikse WS, Bongers EM, Roofthooft MT, et al.TBX4 mutations(small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension.J Med Genet, 2013, 50:500-506.
13.	Maloney JP, Stearman RS, Bull TM, et al.Loss-of-function thrombospondin-1 mutations in familial pulmonary hypertension.Am J Physiol Lung Cell Mol Physiol, 2012, 302:L541-L554.
14.	Germain M, Eyries M, Montani D, et al.Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension.Nat Genet, 2013, 45:518-521.
15.	Upton PD, Morrell NW.The transforming growth factor-β-bone morphogenetic protein type signalling pathway in pulmonary vascular homeostasis and disease.Exp Physiol, 2013, 98:1262-1266.

1. Schermuly RT, Ghofrani HA, Wilkins MR, et al.Mechanisms of disease:pulmonary arterial hypertension.Nat Rev Cardiol, 2011, 8:443-455.
2. Benza RL, Miller DP, Barst RJ, et al.An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry.Chest, 2012, 142:448-456.
3. Hurdman J, Condliffe R, Elliot CA, et al.ASPIRE registry:Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre.Eur Respir J, 2012, 39:945-955.
4. Gomez-Arroyo JG, Farkas L, Alhussaini AA, et al.The monocrotaline model of pulmonary hypertension in perspective.Am J Physiol Lung Cell Mol Physiol, 2012, 302:L363-L369.
5. Maarman G, Lecour S, Butrous G, et al.A comprehensive review:the evolution of animal models in pulmonary hypertension research; are we there yet? Pulm Circ, 2013, 3:739-756.
6. Lawrie A.A report on the use of animal models and phenotyping methods in pulmonary hypertension research.Pulm Circ, 2014, 4:2-9.
7. 陈晓辉, 翁国星, 林群.一种新型的大鼠肺动脉高压模型.中华实验外科杂志, 2005, 22:882.
8. 卢杰, 李梦涛, 王迁, 等.结缔组织疾病相关肺动脉高压动物模型.中华临床免疫和变态反应杂志, 2009, 3:116-121.
9. Liu D, Morrell NW.Genetics and the molecular pathogenesis of pulmonary arterial hypertension.Curr Hypertens Rep, 2013, 15:632-637.
10. Sztrymf B, Coulet F, Girerd B, et al.Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation.Am J Respir Crit Care Med, 2008, 177:1377-1783.
11. Nasim MT, Ogo T, Ahmed M, et al.Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension.Hum Mutat, 2011, 32:1385-1389.
12. Kerstjens-Frederikse WS, Bongers EM, Roofthooft MT, et al.TBX4 mutations(small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension.J Med Genet, 2013, 50:500-506.
13. Maloney JP, Stearman RS, Bull TM, et al.Loss-of-function thrombospondin-1 mutations in familial pulmonary hypertension.Am J Physiol Lung Cell Mol Physiol, 2012, 302:L541-L554.
14. Germain M, Eyries M, Montani D, et al.Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension.Nat Genet, 2013, 45:518-521.
15. Upton PD, Morrell NW.The transforming growth factor-β-bone morphogenetic protein type signalling pathway in pulmonary vascular homeostasis and disease.Exp Physiol, 2013, 98:1262-1266.

Chinese Journal of Respiratory and Critical Care Medicine

Pathological Changes of Heart and Lung Tissues in Rats with Pulmonary Hypertension Induced by Monocrotaline

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