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Background Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes.How to stabilize vulnerable plaques is still a challenge to medical science.Alprostadil is a biologically active substance with strong activity on vessel.Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.Methods Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age.At week 17,they were divided randomly into groups for treatment with a high dose (3.6 μg · kg-1 · d-1) or low dose (1.8 μg · kg-1 · d-1) of an ALMP,or 0.2 ml/d normal saline (control group).The drug was administered using a micro-capsule pump.Twenty weeks after drug administration,pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed,and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence.The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA,and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR.Thrombospindin-1 (TSP-1) expression was detected using West blotting.Results Compared with the control group,ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P ＜0.01),significantly lowered the contents of the lipid core (P ＜0.01),significantly reduced the number of ruptured fibrous caps (P ＜0.05),and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P ＜0.05).ALMP treatment significantly reduced the expression of MOMA-2,superoxide anion,MMP-9,ICAM-1 and CD40 in the plaques (P ＜0.01),decreased plasma ICAM-1 expression (P ＜0.01),and increased the expression of TSP-1.Conclusions Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.