Establishment of a Wuzhishan minipig model of atherosclerosis induced by high fat/cholesterol diet and regulation of Lp-PLA2 expression / 中国实验动物学报

ABSTRACT

Objective To establish a Wuzhishan minipig model of atherosclerosis(AS) induced by high fat/cholesterol diet,and observe the changes of expression of lipoprotein associated phospholipase A2(Lp-PLA2) in plasma and plaques.Methods 10 Wuzhishan minipigs were randomly divided into 2 groupsThe normal control(Ctr,n=4) group was fed with normal diet,and AS model(n=6) group fed with high fat/cholesterol diet for 24 weeks.After the modeling for 24 weeks,the changes of total cholesterol(TC),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),triglyceride(TG),C-reactive protein(CRP),Lp-PLA2 activity and composition were detected.The changes of vascular lipid deposition and plaques were assessed by pathology using oil red O staining and HE staining,respectively,and immunohistochemical staining for IL-6 protein expression.Moreover,the expression of Lp-PLA2 mRNA determined by RT-PCR and protein by Western blot were observed in the abdominal aortic tissues.Results Compared with the control group,the body weight,body mass index(BMI),TC,LDL-C,HDL-C,CRP,Lp-PLA2 activity and composition and aortic lipid deposition were significantly increased,and AS plaque formation was observed in the AS model group(P<0.05,P<0.01).The expression of Lp-PLA2mRNA and protein and IL-6 protein in abdominal aortic tissues were also significantly increased(P<0.05).Conclusions Long-term high fat/cholesterol diet feeding for 24 weeks can induce atherosclerosis in Wuzhishan minipigs,and Lp-PLA2 plays a key role in the vascular inflammation and plaque formation.