Effect Of Ruanmailing Oral Liquid On Angiogenesis In Experimental Atherosclerotic Plaque

Objective:Through the observation of the effect of ruanmailing oral liquid onApolipoprotein E-knockout mice in terms of the angiogenesis within atheroscleroticplaques，to explore the mechanisms of the role of ruanmailing oral liquid inplaque-stablilization.Methods:Thirty ApoE-dificient mice of6-8weeks old (C57BL/6J) were fed with highfat diet (Basal diet85.5%, Cholesterol2.0%, pig bile2.5%, lard10.0%). After12weeks until mature atherosclerotic plaques were formed, there independent goupswere set up, including Model group，Ruanmailing group, Simvastatin group, and fedwith medicine for another12weeks (6gene normal mice as control). Blood wasextracted from orbital venous to study the lipid (TC, TG, LDL-C, HDL-C) variation.Then, HE-stain was used to observe aortic pathomorphological changes of mice,meanwhile, immunohistochemical method was adopted to determine the angiogenesisdensity of plagues which is marked by CD105，as well as the expression anddistribution of CD105，VEGF, bFGF in mice aorta. Finally, RT-PCR semi-quantitativewas used to analyse VEGF mRNA expression of aorta.Results:1. Blood Lipid of each team: TG, TC and LDL-C levels of model,ruanmailing and simvastatin groups were significantly higher than those in the controlgroup, and HDL-C level of model and ruanmailing groups were significantly lower(P<0.01). and simvastatin groups was considerable (P>0.05).than the control group’s.Compared with model group, TC, LDL-C，TG levels of ruanmailing and simvastatingroups were significantly lower, however, HDL-C levels were significantly higher (P <0.01, P <0.01).No significance of blood lipid were found between ruanmailing groupand simvastatin group (P>0.05).2. Aortic Pathomorphological Change: The aortic wall of Control group wasthickness even and Lining has not seen the obvious hyperplasia as well as Filmsmooth muscle in orderly rows. However, different degrees of pathological damage inaorta appeared in the other groups, of which the degree of pathological damage islighter in the ruanmailing and simvastatin groups, compared with the model group.3. Microvessel Density of each team: Microvessel density values of modelgroup, ruanmailing and simvastatin groups were significantly higher than that ofcontrol group (P <0.01), and ruanmailing and simvastatin groups were significantlylower than that of model group（P <0.01）. No significance were found betweenruanmailing group and simvastatin group (P>0.05).4. CD105,VEGF,bFGF Protein Expression:CD105Protein Expression: The result of immunohistochemistry dyeingshowed that that the expression of CD105protein of model group was significantlyhigher（P <0.01）and ruanmailing and simvastatin groups were higher（P <0.05）comparing to those of control group，thus comparing to model group the expression ofCD105protein of ruanmailing and simvastatin groups were significantly lower（P<0.01）.No significance were found between ruanmailing group and simvastatingroup (P>0.05)VEGF Protein Expression:The result of immunohistochemistry dyeing showedthat VEGF,protein of the other three groups were highly expressed comparing tothose of control group. And, the expression of VEGF Protein were significantlydecreased （P <0.01） both in ruanmailing and simvastatin groups whilst withconsiderable exprssion level(P>0.05),compared with the model group.bFGF Protein Expression: The result of immunohistochemistry dyeing showedthat the expression of bFGF,protein of model group were significantly higher thusthouse of ruanmailing group were not so high and simvastatin groups wereconsiderable comparing to those of control group. The expression of bFGF Protein were significantly decreased（P <0.01）both in ruanmailing and simvastatin groupswhilst with considerable exprssion level(P>0.05),compared with the model group.5. VEGF mRNA Expression：RT-PCR semi-quantitative result showed thatVEGF mRNA expression in ruanmailing and simvastatin groups significantlydeclined（P <0.01）compared with the model group which presented significantlyhigher VEGF mRNA expession while comparing with the control group（P <0.01）.No significance were found between ruanmailing group and simvastatin group whilethese two groups were considerable with the model group (P>0.05)Conclusion:1. Ruanmailing oral liquid could control lipids metabolism.2. Ruanmailing oral liquid could inhibit the expression of VEGF, bFGF，CD105protein.3. Ruanmailing oral liquid could inhibit the expression of VEGF mRNA.4. Ruanmailing oral liquid could suppress the Angiogenesis within atherosclero-tic plaques to stable plaque thereby delay and inhibit the progress of atherosclerotic.5. The liver and kidney tonify herbs and drugs for supplementing qi and activat-ing blood circulation could could suppress the Angiogenesis within atheroscleroticplaques.