A rat model of sustained hypobaric hypoxia-induced pulmonary hypertension

作者:Zhao, Sheng; Xue, Xinying; Gao, Peiliang; Deng, Hui; Yao, Xiaoyan; Zhang, Jingyuan; Gao, Nana; Cui, Lei; Wang, Yong*; Pan, Lei*; Yang, Shuixiang*
来源:International Journal of Clinical and Experimental Medicine, 2017, 10(2): 3366-3372.

摘要

Objectives: High-altitude pulmonary hypertension (HAPH) is a worldwide public health issue in mountainous areas, while the underlying mechanism of it is still unclear. This study aims to establish a rat model of hypobaric hypoxia-induced pulmonary hypertension through sustained exposure to a simulated high altitude atmospheric environment in plain area. Methods: Twelve healthy male SD rats were randomly and equally divided into a model group and a control group. The model group was housed in an automatic adjusting hypobaric hypoxia chamber for 4 weeks, and the control group was housed under normobaric normoxic condition in the same room. The mean pulmonary arterial pressure (mPAP), right ventricular pressure (RVSP), the right ventricle (RV) weight, left ventricular (LV) weight, interventricular septum (S) weight, right ventricular hypertrophy index (RVHI), hematoxylin-eosinstaining, elastic fibers staining, ratio of the thickness of vascular wall to its outer diameter (MT%), ratio of the cross-sectional area of the middle vascular wall to the total vascular cross-sectional area (MA%), alpha-SMA positive ratio were detected to evaluate the pulmonary hypertension. Results: As compared to that in control group, rats in model group showed significant increases on mPAP (36.39 +/- 4.26 mmHg versus 16.27 +/- 6.99 mmHg, P<0.001), RVSP (45.29 +/- 6.09 mmHg versus 28.12 +/- 4.67mmHg, P<0.001), RVHI (0.44 +/- 0.08 versus 0.18 +/- 0.05, P<0.001), MT% (44.50 +/- 8.96 versus 19.50 +/- 4.88, P<0.001), MA% (64.00 +/- 6.66 versus 40.45 +/- 7.08, P<0.001), alpha-SMA positive% (57.00 +/- 6.87 versus 30.50 +/- 6.83, P<0.001). Conclusion: The rat model of hypobaric hypoxia-induced pulmonary hypertension has been successfully established by automatic adjusting hypobaric hypoxia chamber. Sustained exposure to a low oxygen environment at a simulate-altitude of 5,000 meter for 4 weeks have caused the pathological remodeling of pulmonary vascular walls and pulmonary hypertension, and further led to a series of pathological changes, including right ventricular hypertrophy. This model is easy to be replicated with good reproducibility and can be widely used in further studies.