Study On The Interventional Effect Of Alprostadil On Hyperhomocysteinemia-induced Atherosclerosis In Rats

Objective: To study the interventional effect and mechanism of alprostadil on hyperhomocysteinemia(HHcy)-induced atherosclerosis(AS)in rats.Methods: Thirty-six Sprague Dawley rats were divided randomly into three groups(each with 12 rats,half male and half female): alprostadil group,model group,and blank group.Rats in the alprostadil group received daily subcutaneous injection of homocysteine(Hcy,100mg/kg*d)+ intraperitoneal injection of alprostadil(5?g/kg*d)+ routine diet.Rats in the model group received daily subcutaneous injection of Hcy(100mg/kg*d)+ intraperitoneal injection of saline + routine diet.Rats in the blank group were fed daily with routine diet without any interventional injections.Eight weeks later,the venous blood was taken to measure the serum concentrations of Hcy,SOD(superoxide dismutase)and ox-LDL(oxidation-low density lipoprotein).Blood vessels at the bifurcation of the abdominal aorta and iliac artery were removed,and observed microscopically after fixation with 4% paraformaldehyde,embedding with wax,sectioned and stained with HE.Results:The serum concentrations of Hcy and ox-LDL in the model group and alprostadil group were significantly higher than those in the blank group;the difference was statistically significant(P<0.05).The serum concentrations of Hcy and ox-LDL in the alprostadil group were significantly lower than the model group;the difference was statistically significant(P<0.05).The serum activity of SOD in the model group or alprostadil group was significantly lower than the blank group;the difference was statistically significant(P<0.05).The serum activity of SOD in the model group was significantly lower than the alprostadil group;the difference was statistically significant(P<0.05).In the alprostadil group,like the blank group,the vascular wall was smooth and the intima was continuous without detachment of endothelial cells,there was no vacuolar degeneration in the muscular cells.In the model group,the vascular wall was not smooth,the tunica intima was broken,endothelial cells could be seen detached,and muscular cells with vacuolar degeneration could be seen,which accorded with the early manifestation of AS.Conclusion:(1)The rat model of HHcy could be successfully established by subcutaneous injection of Hcy.(2)Alprostadil can significantly reduce the concentration of serum Hcy,increase the activity of SOD and reduce the level of ox-LDL in the rat with HHcy.(3)Alprostadil can alleviate the intimal injury and inhibit AS formation by probably reducing the level of oxidative stress induced by HHcy.