| Objective: In recent years, people have gradually realized that the long-term hypoxic plateau environment can increase the resistance of the heart to ischemic injury. However, the long-term sustainability of chronic high altitude hypoxia also has many adverse effects to the body, as right ventricular hypertrophy and polycythemia. Numerous studies show that intermittent hypobaric hypoxia not only has cardioprotective effect on the body but also has low adverse effects, at the same time, IHH is a common clinical form of hypoxia, such as coronary heart disease and sleep apnea syndrome. Therefore, IHH is increasing people’s attention. Studies have shown that, IHH has many benefits for the body. For example, it can protect the nerves, liver and other organs. It also has a certain role of adjuvant therapy to chronic obstructive bronchitis and bronchial asthma. It is also reported in the literature that IHH can also has a good effect to ischemia/reperfusion heart dysfunction and arrhythmias and enhance tolerance of the body to ischemia and hypoxia. But no research suggest that IHH has a preventive and protective effect on pulmonary hypertension.In this study, we use monocrotaline induced PAH model on male SD rats. To observed the role of IHH to function and morphology of rat pulmonary vascular, and to explore its protection mechanisms to pulmonary vascular, and to provide new experimental and theoretical basis for clinical.Method: Clean and healthy male SD rats supplied by Hebei Medical University Experimental Animal Research Center, weight from 150 to 200 g.The animal were randomly divided into four groups: the normal control group(con group), pulmonary hypertension group(PAH group), intermittent hypobaric hypoxia treated group(IHH group), IHH+MCT group. The rats in control group without any treatment. Normal feeding 28 days and then tested right ventricular systolic pressure(RVSP) and mean pulmonary artery pressure(m PAP), calculated of right ventricular hypertrophy index(RVHI) and observed changes of vascular reactivity in vascular ring perfusion experiment. The rats in PAH group by intraperitoneal injection of MCT, then measured RVSP and m PAP, calculated RVHI and observed the changes in vascular reactivity after injection 14 days. The rats in IHH group accepted IHH treatment of 5km altitude, 6h a day, and tested RVSP, m PAP, RVHI and observed changes in vascular reactivity after treatment for 28 d. IHH+MCT group standed the IHH 28 d then intraperitoneal injection of MCT, 14 days after the injection then tested of RVSP, m PAP, RVHI and observed changes in vascular reactivity. All the experimental data were used SPSS 13.0 statistical software for statistical analysis. And all the results were data of normal distribution and were expressed as mean±standard deviation. Compare the data of the four group use one-way ANOVA, The test level of was α=0.05, P<0.05 was considered statistically significant.Results: 1 Death of animals and the general growth conditions 1.1 Deaths:PAH group died two rats, the remaining rats were all survived 1.2 General growth conditionsThe rats in PAH group to reduce weight, activity levels and food intake, tired lying, breathlessness than the control group after intraperitoneal injection of MCT 2weeks later. The rats in IHH group had improved in degree of activity, eating and weight status than in the same period of PAH, but worse than normal group. The rats in PAH group were visible right ventricle thickening, lung congestion and swelling, some accompanied pleural effusion, ascites, even pericardial effusion after thoracotomy. 2 Hemodynamic results 2.1 Results of m PAP in each groupMPAP in PAH group was significantly higher than the other three groups, and the differences were statistically significant, IHH+MCT group were significantly lower than PAH group, the difference was statistically significant(IHH+MCT: 19.45±1.03 vs PAH: 35.28±0.94, P<0.05), IHH+MCT group was higher than control group, but it is no statistically significant(IHH+MCT: 19.45±1.03 vs CON: 16.4±0.46, P>0.05). IHH group was higher than control group, but it is no statistically significant(IHH: 17.86±0.42 vs CON: 16.42±0.46, P>0.05). 2.2 The results of RVSP in each groupRVSP in PAH group was significantly higher than the other three groups(PAH: 45.14±0.62 vs CON: 24.46±1.21, P<0.05); IHH+MCT group was significantly lower than PAH group, the difference was statistically significant(IHH+MCT: 27.58±0.98 vs PAH: 45.14±0.62, P<0.05). IHH+MCT group was higher than control group, but it is no statistically significant(IHH+MCT: 27.58±0.98 vs CON: 24.46±1.21, P>0.05). IHH group was higher than control group, but it is no statistically significant(IHH: 25.74±1.16 vs CON: 24.46±1.21, P>0.05). 3 The results of right ventricular hypertrophy index(RVHI)RVHI in PAH group was significantly higher than the other three groups. RVHI in PAH group was significantly higher than control group(PAH: 48.76±11.7 vs CON: 24.43±3.79, P<0.05). RVHI in IHH + MCT group were significantly lower than the PAH group(IHH+MCT: 25.61±4.18 vs PAH: 48.76±11.7, P<0.05), but has not yet reached the level of control group(IHH+MCT: 25.61±4.18 vs CON: 24.43±3.79, P>0.05). IHH group was higher than control group, but it is no statistically significant(IHH: 27.66±4.17 vs CON: 24.43±3.79, P>0.05). 4 The role of hypobaric hypoxia on the pulmonary artery endothelial functionIn the four experimental groups, phenylephrine(PHE, from 10-8mol/L to 10-5mol/L) could cause vascular contractile response, acetylcholine(ACH, from 10-8mol/L to 10-5mol/L) could cause endothelium-dependent vasodilatation, Sodium nitroprusside(SNP, from 10-8mol/L to 10-5mol/L) could cause endothelium-independent vasodilation and all above drugs had a concentration dependent manner on systolic and diastolic reaction of blood vessels.Endothelium-dependent Contractile and vasodilation reaction and endothelium-independent vasodilation response of pulmonary artery in MCT induced PAH rats was significantly impaired than control group, the difference was satistically significant(P<0.05). And IHH intervention could significantly improved endothelium-dependent and endothelium-independent vasodilator relaxation which impaired in PAH group and the difference was satistically significant(P<0.05).Conclusion:1 SD rats can form a model of pulmonary hypertension by intraperitoneal injection of monocrotaline.2 Intermittent hypobaric hypoxia can effectively reduce the elevated mean pulmonary artery pressure and right ventricular systolic pressure in rats with pulmonary hypertension which induced by monocrotaline.3 Intermittent hypobaric hypoxia can effectively reduce hypertrophy of right ventricular in rats with pulmonary hypertension which induced by monocrotaline.4 Intermittent hypobaric hypoxia plays an important protective role to endothelium-dependent Contractile and vasodilation and endoth elium-independent vasodilation response in pulmonary vascular of rats with pulmonary hypertension. |
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