ABSTRACT
AIM:To study the role of amifostine on the formation of benzo [a]pyrene (BaP)-induced abdomi-nal aortic aneurysm ( AAA) in C57BL/6J mice and the underlying mechanism .METHODS: RAW246.7 mononuclear macrophage in vitro were divided into control group , DMSO group, BaP group, low dose (1 μmol/L) amfostine treated group, middle dose (5 μmol/L) amfostine treated group and high dose (25μmol/L) amfostine treated group .The influ-ence of BaP on the expression of matrix metalloproteinase (MMP)-9, MMP-12, TNF-α, NF-κB in the RAW246.7 mono-nuclear macrophages in vitro was determined by Western blot .Male C57BL/6J mice (8 months old) were divided into con-trol group, model group (AngII+BaP group), low dose (50 mg/kg) amfostine treated group and high dose (100 mg/kg) amfostine treated group.After 6 weeks, the abdominal aorta were isolated .The aortic tissues were subjected to HE and Masson staining.The vascular wall structure , infiltration of macrophage , the expression of MMP-9, MMP-12, TNF-α, NF-κB were evaluated by Western blot and immunochemistry staining .RESULTS:Amifostine attenuated BaP-induced expres-sion of TNF-α, MMP-9, MMP-12, NF-κB in the RAW246.7 mononuclear macrophages (P<0.05).The results of animal experiments showed that the incidence of AAA in high dose amifostine treated group were significantly lower than that in low dose amifostine treated group and model group (P<0.05).Immunohistochemistry staining observation showed that amifos-tine inhibited the aortic macrophage infiltration more obviously in high amifostine treated group compared with model group and low dose amifostine treated group (P<0.05).Compared with model group and low dose amifostine treated group , the MMP-9, MMP-12, TNF-αand NF-κB expression of abdominal aorta in high amifostine treated group was reduced signifi -cantly ( P<0.05 ) .CONCLUSION: Amifostine inhibits BaP-induced activation of macrophages , and also prevents the formation of abdominal aortic aneurysm in C 57BL/6J mice induced by BaP by inhibition of the NF-κB pathway, macro-phage infiltration and the expression of TNF-αand MMPs.