Study On The Mechanism Of Experimental Animal Pregnancy Complicated With Pulmonary Hypertension Aggravating The Symptoms Of Hypoxic Pulmonary Hypertension In Their Offspring

Pulmonary Hypertension（PH）is a clinical symptom caused by pathological mechanisms such as thickening of the small arteries of the lungs and continuous pulmonary vasoconstriction.It is characterized by pulmonary vascular resistance（PVR）and pulmonary artery pressure（PAP）progressive increase.The diagnostic criteria are:mean Pulmonary Artery Pressure（m PAP）>20 mm Hg（1mm Hg=0.133 k Pa）measured by Right Heart Catheterization（RHC）at sea level and resting state.The mortality of this disease is high,the pathogenic mechanism is not yet fully understood,and there is no effective cure method.The epidemiological survey of PH shows that the incidence of PH in women is 4 to 5times higher than that in men.Especially for women of childbearing age with recent pregnancy history,the incidence of PH is even higher than that of the general female population.However,the impact of maternal PH and the various symptoms or pathophysiological changes（such as hypoxia）caused or accompanying on the long-term health of the fetus in adulthood is still unclear.In order to explore the sensitivity of the offspring of PH patients to hypoxia-induced PH,this paper uses the PH model of rats and mice,respectively,and examines the right ventricular systolic pressure（RVSP）of each group of experimental mice through RHC and right ventricular dissection.paraffin sections were made and H&E staining and immunofluorescence experiments were performed to determine the degree of remodeling of the pulmonary blood vessels and arteries of the experimental rats in each group.The proliferation rate of medial cells and the degree of vascular muscularization have preliminarily explored the susceptibility of the offspring of the PH model of rats and mice to hypoxic PH.The main results are as follows:（1）Hypoxia can significantly increase the RVSP,RVHI,pulmonary vascular media thickness and blood indexes of pregnant rats.After the end of hypoxia in pregnant rats,RHC,right ventricular dissection,blood vessel thickness statistics in H&E slice and blood routine techniques were used to detect the occurrence and development of PH in rats,and it was found that hypoxia exposure can significantly increase the RVSP of rats（P<0.01）,RVHI（P<0.01）,pulmonary vascular media thickness（P<0.05）and blood indicators（P<0.05 or P<0.01）.（2）Compared with the control group,hypoxia further enhanced the RVSP,RVHI,pulmonary vascular media thickness,pulmonary vascular muscularization and media cell proliferation of the offspring of the PH pregnant rats.After the adult offspring（7 weeks of age）were exposed to hypoxia,RHC,right ventricular dissection,blood vessel thickness statistics in H&E slice and immunofluorescence（IF）were used to measure the severity of PH in offspring,and it was found RVSP（P<0.01）,RVHI（P<0.001）,pulmonary vascular media thickness（P<0.05）,pulmonary vascular muscularization（P<0.001）,and media cell proliferation（P<0.001）of offspring rats under hypoxia,compared with the hypoxic control group,were all significantly higher.（3）egln1/2/3^EC+/-mice spontaneously aggravated RVSP,RVHI,pulmonary vascular remodeling and muscularization.After egln1/2/3^EC+/-mice normally grow to 12 weeks of age,RHC,right ventricular dissection,vessel thickness statistics in H&E sliceand IF technology were used to detect the PH severity of egln1/2/3^EC+/-mice,and egln1/2/3^EC+/-mice was found spontaneously significantly increased RVSP（P<0.001）,RVHI（P<0.01）,pulmonary vascular remodeling（P<0.05）and the degree of muscularization（P<0.05）.（4）Compared with the control group,hypoxia further aggravated the RVSP,RVHI,pulmonary vascular media thickness,pulmonary vascular muscularization,and media cell proliferation of wild-type offspring of egln1/2/3^EC+/-mice.Technical indicators such as RHC,right ventricular dissection,H&E slice vessel thickness statistics,and IF found that the RVSP（P<0.05）,RVHI（P<0.05）,and pulmonary vascular media thickness（P<0.05）of offspring mice under hypoxia),pulmonary vascular muscularization（P<0.001）and media cell proliferation（P<0.001）were all significantly higher than those in the hypoxic control group.In summary,the progeny of the PH experimental mouse model are more sensitive to hypoxia and are prone to develop more severe hypoxic PH,and this progeny mechanism may not depend on the mother’s hypoxic exposure during pregnancy.