The Effect Of Exogenous Superoxide Dismutase On Pulmonary Arterial Remodeling In Pulmonary Hypertension Rats

Objective: Pulmonary arterial hypertension（PAH）has been a hot researchtopic，in cardiovascular diseases, the clinical pathological tissue are difficult toobtain, to establish animal pathological model and taking the model asexperimental objects become the most important experimental method.Theimportant pathologic basis of pulmonary hypertension is pulmonary vascularremodeling and pulmonary vascular remodeling, the premise is the cell damage,repair, proliferation, although domestic and foreign scholars have conducted alot of research, but the exact mechanism of cell proliferation cascade notcompletely illustrated.Studies have shown that antioxidant imbalance systemstress reaction and oxidation in cells is one of the importantmechanisms.Superoxide dismutase (SOD) is a group of specific metal protein, anumber of studies have demonstrated, has protective effects on the ischemiareperfusion injury, inflammatory reaction. This experiment through theestablishment of a rat model of pulmonary hypertension tail vein injection ofexogenous superoxide dismutase (Exterior SOD), to investigate the effect ofSOD on pulmonary vascular remodeling, for clinical drug therapy for pulmonary arterial hypertension and provide more theoretical basis.Methods:45male SD rats were randomly divided into3groups: control group(n=15), surgery group (n=15) and surgery+exogenous superoxide dismutase(n=15). After40days, we measured the mean pulmonary artery pressure (mPAP)of rats in all groups by right cardiac catheterization;Collect the blood for bloodtotal reactive oxygen species (ROS), nitric oxide (NO), carbon monoxide (CO),and malondialdehyde (MAD) detection;The rats were sacrificed to cut thenecessary experimental organization and specimen,we also measured the rightventricular/body weight (right ventricle/body weight, RV/BW) and the rightventricular hypertrophyindex (RVHI);Cut the pulmonary tissue, paraffin sectionand HE staining technique, optical microscope observation of changes inpulmonary vascular structural changes, application of image analyzer, onvascular muscularization of pulmonary artery for quantitative calculation;Isolation of the pulmonary artery, homogenate;TUNEL detection method todetect pulmonary cell apoptosis of rats with application of DNA fragment endlabeling；Part of homogenate extraction of manganese superoxide dismutase(MnSOD), copper zinc superoxide dismutase (Cu-ZuSOD), glutathioneperoxidase (mRNA GPx), application of real-time fluorescent quantitative PCR(RT-PCR) technique for the detection of gene expression.Results:(1) The process of modeling, no rat died, postoperative rats recoveredrapidly, there is no obvious difference between general observation.(2) Compared with the normal group, carotid artery jugular veincannula shunt group, common carotid artery and external jugular vein cannulashunt group+SOD, after40d, the determination of serum MOD value, mPAPvalue, RV/BW ratio and RVHI index were significantly higher than those in thecontrol group, and the determination of plasma NO, CO were significantly low in the control group, the simple operation group rats, the above indexes andoperation in+SOD group, two groups of data, there is a big difference, thedifference has statistical significance(P<0.05).(3) Compared with the normal control group, model group2aftervascular pulmonary hypertension rats tube wall thickness of vascular diameter(WT%), vascular wall area accounted for total cross-section area percentage(WA%) was higher than that of control group (P<0.05), including operation,+SOD group was significantly higher than the operation group, the differencewas statistically significant (P<0.05).(4) compared with the control group, shunt pulmonary tissuemitochondria membrane group rats swelling, mitochondrial activity decreased;manganese superoxide dismutase pulmonary vascular tissues (MnSOD), copperzinc superoxide dismutase (Cu-ZuSOD), glutathione peroxidase (GPx)expression, operation in+SOD group was significantly higher than the controlgroup and the operation group, and operation group data was lower than that ofnormal control group, and the mitochondrial membrane operation the rats ofgroup+SOD swelling slighter than the operation group, activity had differentdegrees of recovery, and the apoptosis rate was decreased, the difference wasstatistically significant (P<0.05)Conclusion:(1)common carotid artery and external jugular vein shunt methodto establish the model of casing pressure of pulmonary artery, rats appearedright ventricular hypertrophy and pulmonary vascular remodeling phenomenon,show the common carotid artery and external jugular vein cannula shunt methodcan serve as an effective model of pulmonary arterial hypertension.(2) Exogenous superoxide dismutase (SOD) through itsantioxidant effect, and activate the body’s own synthesis of antioxidant proteins such as MnSOD, CuZnSOD, GPx antioxidant enzyme gene expression andenhance its antioxidation, relieve stress, prevent cell damage, excessivehyperplasia, delay the development progress of pulmonary arterialhypertension，the mechanism may lie in the repair of oxidative stress caused bybiological membrane and biological macromolecular damage.