| Objective:By establishing a monocrotaline combined with abdominal aorta-inferior vena cava fistula surgery in high pulmonary blood flow pulmonary hypertens ion rat model to investigate the effect of survivin inhibitor YM155 on pulmonary artery smooth muscle cell proliferation and apoptosis in vivo.Methods:Thirty male Sprague-Dawley(SD)rats aged 8-9 weeks were randomly divided into a control group,a model group and an intervention group with 10 rats in each group.(1)in the control group,20% ethanol solvent was injected subcutaneously with on-off operation;(2)in the model group,1% monocrotaline solution was injected subcutaneously,after 1-week abdominal aorta-inferior vena cava fistula was performed to established a model of pulmonary hypertens ion with high pulmonary blood flow,(3)In the intervention group,after being modeled,a survivin inhibitor 1% YM155 solution was given for 2 weeks.Each group of rats was fed under the same condition for 5 weeks.Right ventric les pressure was measured,and calculate the right heart hypertrophy index.The HE staining of lung tissue was observed under light microscope to compare the general differences of each groups.The immunohistochemical method used to detect The expression of survivin protein in pulmonary artery,the PCNA method was used to detected the proliferation rate of pulmonary arterial smooth muscle cells,and the TUNEL method was used to detect the apoptosis rate of pulmonary artery smooth muscle cells.Pulmonary arterial smooth muscle cells from each group were used to culture primary pulmonary arterial smooth muscle cells;the expression of survivin mRNA in pulmonary arterial smooth muscle cells was detected by qRT-PCR,and the expression of survivin protein was detected by western blot.Results:(1)Average right ventricular pressure: The average right ventricular pressure(37.48±1.89 mm Hg)in the model group was significantly higher than that in the control group(15.30±1.19 mmHg),with statistically significant(P<0.05).The pressure in the interventional(27.10±1.93 mmHg)was lower than the model group with statistically significant(P<0.05).(2)Right ventricular hypertrophy index: Right ventricular hypertrophy index(40.63±1.60%)in the model group was significantly higher than that in the control group(23.40±1.45%),(P<0.05).Right ventricle hypertrophy index in the intervention group(30.85±2.13%)was lower than the model group,(P<0.05).(3)HE staining of lung tissue: The pulmonary arterioles of the model group were markedly muscularized and thickened to varying degrees,the lumen was stenotic or nearly occluded,and inflammatory cells infiltrated around the blood vessels;the pulmonary arterioles of the intervention group were visible.The vascular wall was muscularized with slight thickening.There was no obvious stenosis in the lumen,and there was a small amount of inflammatory cell infiltration around the blood vessel.No abnormalities were seen in the control group.(4)Expression of survivin protein in pulmonary arteries: The optical density of the model group was 4.27±0.90,and the intervention group was 1.40±0.45.There was a statistically s ignificant difference between the two groups(P<0.05).No expression was found in the control group.(5)Pulmonary arterial smooth muscle cell proliferation rate and apoptosis rate:The proliferation rate of the intervention group(22.25±2.71)% was significantly lower than that of the model group(35.03±2.41)%,and the difference was statistically significant(P<0.05).The apoptotic rate of the intervention group was(30.92±2.39)% Compared with the model group(10.12±1.47)%,the intervention group was significantly higher than the model group,and the difference was statistically significant(P<0.05).(6)The expression level of survivin mRNA in pulmonary artery smooth muscle cells : The relative expression level in the model group was 1.35±0.09,and the relative expression volume in the intervention group was 0.41±0.06.There was no expression in the control group.Compared with the model group,the intervention group was significantly lower than the intervention group.In the model group,the difference was statistically significant(P<0.05).(7)Expression level of survivin protein in pulmonary arterial smooth muscle cells : The relative expression level in the model group was 1.36±0.12,and the relative expression amount in the intervention group was 0.43±0.08.There was no expression in the control group.The intervention group was significantly lower than the model group in the intervention group.In the model group,the difference was statistically significant(P<0.05).Conclusions : 1.YM155 can inhibit the expression of survivin in pulmonary artery smooth muscle cells in rats with high pulmonary blood flow pulmonary hypertens ion in vivo;2.In vivo with YM155 can inhibit the proliferation of pulmonary artery smooth muscle cells and promote apoptosis in rats with high pulmonary blood flow pulmonary hypertension,and improve pulmonary vascular remodeling... |
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