The Protective Effect And Potential Mechanisms Of Alprostadil Injection On No-reflow Phenomenon After Myocardial Ischemia-reperfusion In Rats

Objective: To observe the protective effect of alprostadil injection on no-reflow aftermyocardial ischemia-reperfusion in rats and explore its potential mechanisms.Methods:150male Wistar rats were randomly divided into six groups and each group has25rats. The Sham group and Model group were given sodium chloride injection5mL/kg byintravenous injection, Alprostadil groups were intravenously injected alprostadil injection2,4,8μg/kg respectively and the positive drug group was given nitroglycerin2mg/kg byintravenous injection. Every group was given intravenous injection after ligation andreperfusion immediately.After the end of reperfusion each group was tested: RA/LVA, MIA/RA, NA/RA; CK-MB,LDH, AST, MPO, SOD activity and serum MDA, PGI2, TXA2, NO, TNF-α, IL-6levels;morphological changes in myocardial tissue and myocardial ultrastructural changes.Results:①Compared with the Sham group, RA/LVA, MIA/RA and NA/RA in the Modelgroup were significantly increased (P<0.01or P<0.001). Compared with Model group,Alprostadil4,8μg/kg groups could significantly reduce RA/LVA, MIA/RA and NA/RA.②Compared with the Sham group, serum NO content and MDA content of the Model groupdecreased significantly（P<0.01）, MPO activity increased significantly（P<0.01）, while SODactivity was significantly lower(P<0.01). Compared with the Model group, Alprostadil2,4,8μg/kg groups could significantly reduce serum MPO activity(P<0.05or P<0.01), significantlyincrease serum NO(P<0.05or P<0.01), alprostadil4,8μg/kg groups could increase SODactivity (P<0.05), decrease MDA content(P<0.05or P<0.01).③Compared with the Shamgroup, serum CK-MB, LDH activities of the Model group increased significantly(P<0.001),whereas there is no significant change in the activity of AST. Compared with the Model group,alprostadil4,8μg/kg groups could reduce serum CK-MB, LDH activities(P<0.05).④Compared with the Sham group, plasma TXA2in rats was significantly higher, PGI2was decreased(P <0.01), whereas serum TNF-α, IL-6showed no significant change. Compared withthe Model group, alprostadil4,8μg/kg groups can significantly reduce plasma TXA2, whilePGI2content increased(P<0.05or P<0.01).⑤Compared with the Sham group, myocardialtissue and cardiac myocyte of the Model group were significantly pathological damaged.Compared with the Model group, alprostadil2,4μg/kg groups had no significant difference inpathological changes, but alprostadil8μg/kg group reduced pathological damages ofmyocardium and myocardial cells.Conclusion: Alprostadil injection has a protective effect on experimental myocardialischemia-reperfusion no-reflow phenomenon. The possible mechanisms are: inhibition ofplatelet adhesion and aggregation, increasing the openness of coronary and inhibiting highblood viscosity state, preventing thrombosis, reducing the extent of myocardial oxidativedamage and increasing the body’s antioxidant capacity.