The Role Of Wnt3a/β-catenin/Survivin Pathway In PAH-rats

Background：The cause of Pulmonary arterial hypertension (PAH) remains unknown.Currentresearches show that Pulmonary arterial hypertension is characterized by genetic andacquired abnormalities that suppress apoptosis and enhance cell proliferation in thevascular wall. Inhibition of the inappropriate expression of survivin that accompanieshuman and experimental PAH is a novel therapeutic strategy that acts by inducingvascular mitochondria-dependent apoptosis.In this research,we will investigatewhether survivin play a important role in PAH,and whether survivin could inducecells priferate in lungs of PAH-rats through the wnt/β-catenin pathway from molecularlevel.Methods：Fourty-eight adult male Sprague-Dawley rats (200-220g) divided into twogroups: PAH group (n=24): They were injected moncrotaline (MCT,50mg kg-1),control group (n=24):They were injected same amount of saline.They are all takedDoppler every one day to observe the right heart system. The7days,10days,21daysafter injecting, mean pulmonary artery pressure (mPAP) was measured by the rightheart catheterization, the right ventricle/left ventricle plus septum weight (RV/LV+S)was measured，lung tissues were removed the and taked HE staining, then measuredWA%and WT%of the small arteries of the lung which used IPP6.0software, theresults determine whether the model established successfully. Experimental data tomean+standard deviation, the experimental results of single factor analysis of varianceor t-test, P <0.05was statistically significant with SPSS14.0statistical software.Result:(1)21days after injecting Monocrotaline, there is a significant difference betweenthe two groups in mPAP, RV/LV+S, WA%,WT%,so the model is successful.(2)There is significant difference between the two groups in the protein of wnt3a、β-catenin、survivin of the lung tissue,and survivin only express in the PAHs.mPAPshows significant different begin in the10th days,and RV/LV+S shows significant different begin the21th days.(3) As the times after injecting Monocrotaline,Pulmonary vascular diametergradually widened, right cardiac index is gradually increasing.The10th day is agrowth peak of survivin and tricuspid regurgitation in the same time.Conclusion:The signaling pathway of wnt3a/β-catenin/survivin may cause irreversiblevascular remodeling in the PAH-rats through regulate the apoptosis and proliferation ofsmooth muscle cells.