The Intervention Of Fluoxetine On The Expression Of 5-HTT MRNA In The Lung Tissue Of The Rats With High Altitude Pulmonary Hypertension

Objective High altitude pulmonary hypertension(HAPH) is a serious disease at high altitude,but pathogenesis of HAPH is still not clear, and there is no effective treatmentmethods. vasoconstriction and remodeling is the basic pathology of pulmonary hypertension. Research shows that 5-hydroxytryptamine(5-HT) can induce vasoconstriction and remodeling which is internalized by 5-HT transporter(5-HTT). To observe the expression of 5-HTT mRNA in the lung tissue of the rats with HAPH and the expression of 5-HTT mRNA after returning to the plain. we further study the expression of 5-HTT mRNA in the lung tissue of the rats with HAPH when rats are gastric gavaged with fluoxetine.We hope this project can provide a new treatment of experimental data and ideas for High Altitude Pulmonary Hypertension. Methods 220 male Wistar rats were randomly divided into normal groups (N,n=10), without intervention groups (W,n=70), distilled water control groups (C,n=70), and fluoxetine groups (F,n=70).The N group were fed in the normal conditions , While the remaining groups were placed in a hypobaria and hypoxia chamber simulated to an altitude of 5000 meters with pressure: 0.53 * 105 pa,oxygen pressure: 42mmHg. In addition,the F groups rats were gastric gavaged with fluoxetine (3㎎·kg-1·d-1),the C groups rats were gastric gavaged with distilled water by weight. TheW,C and F groups were placed in hypobaric hypoxia chamber for 30 days, and then placed in the plain.10 rats in each group were dected in 10,20,30days and 10,20,30,90days after returning to the plain.The expression level of 5 - HTT mRNA were examined by RT - PCR in the lung tissue of the rats.Results Compared with N(0.12±0.02), the expression of 5 - HTT mRNA was upregulated after 10 days in the W group (0.35±0.03), and its expression increased with the extension of time in the hypobaria and hypoxia chamber W20d (0.61±0.04)),W30 (0.92±0.03). There was no significantly difference between C groups and W groups in each time.Compared with C10d,C20d,the expression level of 5 - HTT mRNA were significantly lower in F10d ,F20d ( P < 0.01), but there are no difference between F30d and C30d (P > 0.05).After returnning to the plains, there are significantly difference between W20d and W10d,W30d and W20d,W90d and W30d, (0.57±0.02/0.88±0.03,0.38±0.02/0.57±0.02,0.14±0.04/0.38±0.02,all P <0.01);while there is no significantly difference between W10d and W30d which are in the hypobaria and hypoxia .F groups and C groups are also no significantly difference in each time.Conclusions The expression level of 5-HTT mRNA was upregulated in the lung tissue of the rats with HAPH.Fluoxetine can inhibit the expression of 5– HTT mRNA in the lung tissue for short-term.After returnting to the plains,the expression level of 5-HTT mRNA was decreased in the lung tissue, and the intervention of Fluoxetine was not obvious for long-term.