Effect Of Corilagin On Experimental Atherosclerosis And Expressions Of ICAM-1 And VCAM-1 In Atherosclerotic Plaques Of Minipigs

Objective:To investigate the therapeutic effect of Corilagin on atherosclerosis in minipigs.And to observe the regulation effect of Corilagin on the expressions of ICAM-1 and VCAM-1mRNA and protein in atherosclerotic plaque tissue.It provides theoretical and experimental basis for clinical application of Corilagin in treatment of AS.Methods:1.The AS model was duplicated by feeding high-fat and high-cholesterol diet after carotid artery balloon injury in minipigs2.Lipid accumulation and plaque in common carotid artery of AS minipigs were observed by oil red O staining.Hematoxylin-eosin(HE)staining was used to examine morphological changes of common carotid artery in AS minipigs.3.Serum triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected by automatic biochemical analyzer.4.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to determine the effects of Corilagin on the mRNA expression levels of ICAM-1 and VCAM-1 in AS plaques of minipigs.5.Immunohistochemical(IHC)and Western blot methods were used to examine the effects of Corilagin on the protein expression levels of ICAM-1 and VCAM-1 in AS plaques of minipigs.Results:1.The histopathological examinations showed that the common carotid artery presented obvious AS pathological changes.The intima of blood vessels are thickened and visible lipid plaques could be observed.The intima and tunica media of common carotid artery with a large number of foam cell.The above results suggested that the AS model was successfully duplicated.2.Compared with the sham group,the levels of TC,TG and LDL-C in serum were in-creased significantly in the model group,the levels of HDL-C were reduced significa-ntly.Corilagin at 4,2 and 1 mg/kg could markedly decrease levels of TC,LDL-C and TG in serum,but had no effect on HDL-C.3.Compared with the model group,Corilagin at 4 and 2 mg/kg and simvastatin positive control(2mg/kg)lesions were weaker than the model group after 12 weeks of administration.Severity of carotid artery lesion and the levels of lipid plaques and foam cells were reduced.4.The results of RT-qPCR showed that the high-dose group and middle-dose group of Corilagin could significantly down-regulate the expression of ICAM-1 and VCAM-1 mRNA.5.The results of Western blot showed that the high-dose group,middle-dose group of Corilagin could significantly down-regulate the expression of ICAM-1 and VCAM-1 protein.6.Immunohistochemical results showed that compared with the the sham group,the positive reactions of ICAM-1 and VCAM-1 enhanced and the IPP mean dengsity were increased in the model group;compared with the model group,the high-dose group and the medium-dose group of Corilagin could markedly suppress the positive reaction and decrease the IPP mean dengsity.Conclusions:1.Corilagin had obvious effects against the experimental atherosclerosis in AS minipigs,which can improve the degree of atherosclerosis,reduced vascular intimal injury,ruduce TG,TC and LDL-C,and had a dose-effect relationship.2.Corilagin could significantly down-regulate the expression of ICAM-1 and VCAM-1 mRNA and protein in AS plaques of minipigs.