| Background As we know,on the basis of vulnerable plaques,plaque disruption and thrombosis is the main physiological base in acute coronary syndromes(ACS).The episode of ACS is not only caused by stenosis but also by the rupture of an vulnerable plaque and the subsequent thrombus formation.So it is very important to search for the methods of stabilization of plaque.A recent study showed that lectin-like oxidized low density lipoprotein receptor-1 (LOX-1),a novel class of a receptor for atherogenic ox-LDL,facilitates the uptake of ox-LDL and mediates several of the biological effects of ox-LDL in endothelial cells.Ox-LDL activates LOX-1 and induces endothelial dysfunction/ apoptosis,activates the inflammatory reaction and atherosclerosis-associated features in endothelial cells.In addition,ox-LDL can cause the release of matrix metalloproteinases(MMPs)without significant effect on tissue inhibitors of metalloproteinase(TIMPs).This may be the basis of the rupture of soft plaque in ACS.Basic and clinical research has confirmed that Tongxinluo can improve endothelial function,decrease serum lipid and increase the stability of atherosclerosis(AS).However,up to now,there's no research about the effect of Tongxinluo on the signal path of LOX-1 in AS.Objectives(1)To observe the curative effect of Tongxinluo on vulnerable plaques of AS.(2)To identify the role of Tongxinluo to LOX-1 and its signal way. Methods 50 rabbits were randomly divided into the normal group(n=12) and AS group(n=38).AS group were underwent balloon-induced abdominal aortic wall injury and then fed a dietary of 1%cholesterol.After 10 weeks of intervention,these rabbits were randomly divided into regression group(n=12),tongxinluo group(n=11)and simvastatin group(n=11).At the end of week 24, recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques and plaque rupture was triggered by the intra-arterial viper venom and histamine.Serum lipids,hs-CRP were measured and high frequency duplex,acoustic densitometry,intravascular ultrasound(IVUS)and pathologic staining were performed.The level of RAM11,C1,C3,P53,LOX-1,NF-κB,ICAM-1,MMP-1,MMP-3,MMP-9 were measured by means of immunohistochemistry and the mRNA level of LOX-1,VCAM-1,MMP-1 were measured by RT-PCR.Results Compared with the regression group,TC,LDL-C,hs-CRP(P< 0.01),IMT(P<0.05,P<0.01)in the tongxinluo group and simvastatin group were lower and the AIIc%(P<0.05,P<0.01)were significantly higher;in addtion, IVUS showed that PA and PB%(P<0.05,P<0.01)were significantly higher.The comparison between the two simvastatin group and tongxinluo group showed TC(P<0.01),TG(P<0.05)and PA(P<0.05)in the simvastatin group were significantly lower than that in tongxinluo group.The immunohistochemistry showed there are more positive cells of RAM11,P53,LOX-1,NF-κB,ICAM-1,MMP-1,MMP-3,MMP-9 and less C1,C3 in the regression group than that in tongxinluo group and simvastatin group.There are no significant difference between tongxinluo group and simvastatin group.RT-PCR showed the mRNA level of LOX-1,VCAM-1,MMP-1 in the regression group are higher than that in tongxinluo group and simvastatin group(P<0.05,P<0.01).But there is no significant difference between the two intervention groups.Conclusions(1)Tongxinluo can decrease the serum lipid and inflammatory reaction,inhibit apoptosis,decrease the synthesis of extracellular matrix,thus stabilize the vulnerable plaques.There is no significant difference between the effect of tongxinluo group and simvastatin group.(2)Tongxinluo can increase the stability of the vulnerable plaques through affect the critical factors in the signal path of LOX-1. |
PDF Full Text Request