| Objective: To explore the changes of pulmonary vascular remodeling from hypobaric hypoxia environment, and to investigate the effect of fluoxetine, 5 - serotonin inhibitor, on hypoxic pulmonary vascular remodeling in low-pressure hypoxia induced rats.Methods: 326 Wistar rats were randomly divided into 4groups: normal control group (group N, n= 25); no treatment group (group C, n=98); distilled water group (group W, n=98), fluoxetine group (group F, n=105). Rats in group C, W and F were divided equally into 7 subgroups. Subgroups 1-3 were sacrificed after staying in high-altitude environment for 10d, 20d and 30d respectively. Subgroups 4-7 were taken back to low-altitude environment for 10d, 20d, 30d and 90d respectively after staying on plateau environment for 30d. To establish high-altitude induced pulmonary hypertension model, Wistar rats in group C, W and F were kept in hypobaric hypoxia cabin (air pressure: 0.53*105 KPa; oxygen partial pressure 42mmHg) to simulate the environment of 5000 meters altitude. During this period, each rat in group F were treated with 6ml/kg·d (0.5mg/ml) fluoxetine, and Group W, with distilled water 6ml/kg·d. All rats were sacrificed and the right lung were fixed in 10% formalin for 1week, then paraffin slides were prepared and stained with HE and massion. The changes of the percentage of muscular artery (MA), partially muscular artery (PMA), nonmuscular artery (NMA) were observed with 200×microscope. For 400×microscope imaging of muscular pulmonary arteriole accompanying respiratory bronchioles and alveolar duct, imaging analysis were made to calculate the thickness of the tunica media, the perimeter of endarterium and tunica adventitia, the size of insider and outside diameter, the area of lumens, vessels and vessel wall. Then the percentage of the thickness of vessel wall to outer diameter (WT%) and the percentage of the area of vessel wall to that of vessel (WA%) were calculated. Results: The MA of Group C was ascending gradually during kept in high-altitude environment 0-30d. However, NMA was descending and PMA kept dynamic balance. WT% and WA% increased in 20d and 30d compared with 0d. After rats of group C were back to low-altitude environment for 0d- 90d, MA decreased and NMA increased gradually, and MA and NMA recovered to the level of normal control. PMA still kept dynamic balance. WT% and WA% decreased significantly after back to low altitude for 20d or 30d compared to 0d. WT% and WA% recovered to that of group N after back to low altitude for 90d. MA and NMA of group F and group W changed greatly when kept in high-altitude environment the same time of 10-30d, group W increased more than group F.The difference of group C and group W wasn't significance obviously. The difference of WT% and WA% of two groups was significantly during kept in high-altitude environment the same time of 20d, 30d, group W increased more than group F. MA, WT% and WA% of group F on back to low altitude 10d were higher than that of high altitude 30d only. MA of group F decreased gradually during back to low altitude for 20-90d. On the contrary, NMA showed increasing tendency. WT% and WA% of group C, group W group F decreased gradually, and recovered to that of group N when back to low altitude for 90d.Conclusion: Hypoxic pulmonary vascular remodeling aggravated with prolonged low-pressure hypoxia, and gradually returned to normal levels with prolonged plain living, back plain after the long-term hypoxia 30d, hypoxic pulmonary vascular remodeling recovered obviously. During hypobaric hypoxia environment the time of 10d were the evolutional process of non-mus -cular artery to muscular pulmonary artery. Fluoxetine have effects of intervention on hypoxic pulmonary vascular remodeling. Vascular wall of fluoxetine group thicken after stopping the drugs intervention in the short term of return plain. Long-term hypoxia lead to the extracellular matrix (elastic and collagen fibers) increased. |
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