Study On The Changes Of TGF 1 And MiRNA Expression In Lung Tissue Of Mice With Pulmonary Arterial Hypertension

Objective: the relationship between animal experiments clear lung TGF-?1 and MiRNAs expression and the formation of pulmonary hypertension and vascular remodeling,determine whether the speed of progress in pulmonary arterial hypertension,so as to provide the early diagnosis of CHD-PAH(congenital heart disease related pulmonary Arterial hypertension)Methods : to establish a mouse model of pulmonary hypertension,and to study the influence of hemodynamic changes on the expression of TGF-?1 and miRNAs.Methods: 20 male C57 mice were randomly divided into 2 groups: A1,A2,A1 was the experimental group,A2 was sham operation group.Two groups were treated with pentobarbital sodium 40mg/kg intraperitoneal anesthesia.The experimental group 3 left intercostal thoracotomy and resection of the left lung,the sham operation group 3 left intercostal thoracotomy,do not resection of left lung.At 8 weeks after surgery,.The experimental group and sham operation group were measured for right ventricular systolic pressure(RVSP)and right ventricular(RV)and left ventricular(LV)+ ventricular septal(SP)mass,and right ventricular hypertrophy index(RVHI)was calculated.A1,A2 of the right lung were performed HE staining for pathological analysis to determine whether the model conforms to the physiological and pathological changes ofPAH,with immunohistochemical detection of TGF-? 1 expression in pulmonary artery,qRT-PCR were used to detect the expression of TGF-? 1 and miRNAs.Results:(1)experimental group compared with the sham operation group,The RVSP of experimental group is 49.7 + 6.82 mmhg,and RVHI of experimental group is 20.3 ± 4.53 mmhg,The RVSP of the sham operation group is 20.3±4.53 mmhg and RVHI of the sham operation group is 0.199±0.03(P<0.0l),Compared with the sham operation group,the experimental group RVSP and RVHI were significantly increased.The experimental group under the microscope,vascular endothelial hyperplasia,microaneurysm small,pulmonary vascular occlusion,machine,pulmonary smooth muscle layer and outer layer of elastic fibers were significantly thickened,membrane thickening,vascular cavity decreases,pulmonary artery cross-sectional area is 3,TGF-?1protein expression in the experimental group was significantly higher than the sham operation group(P<0.05).(2)In the lung tissue of the experimental group in the animal model of TGF-?1 amplification multiples of 1-3 times of the sham operation group,the lung tissue in the experimental group,the expression of miRNA-19 a in 15-30 times higher than that of the sham operation group,the expression of miRNA-18 a increased 1-4 times,the expression of miRNA-23 a increased 1-2.5times,the expression of miRNA-25 a increased 1-3times(P<0.05).The expression of miRNA-19 a in experimental group was significantly higher than that of other miRNAs.Conclusion:The hemodynamic changes caused by left lung resection can lead to the formation of pulmonaryhypertension in mice.The animal model of pulmonary hypertension can be used in the laboratory study of CHD-PAH.The high expression of TGF-1 and miRNA-19 a may be involved in the remodeling of pulmonary vessels and the formation of pulmonary hypertension in the mouse model of pulmonary hypertension.