Study The Effects And Mechanisms Of Simvastatin On An Rabbit Model Of Kawasaki Disease

Objective:To observe the histopathologic characteristics and the Ultrastructure pathologicalfeatures of Coronary Artery vasculitis in rabbit caused by repeated injections of the BovineSerum Albumin(BSA).Methods:Twenty weanling rabbits were randomly and equally divided into treatment groups forBSA or normal saline (NS), and administered the respective treatment by intravenousinjection at day1, day14for two cycles. Six weeks after the first treatment, rabbitsunderwent coronary angiography and coronary arteries were removed within one hour.Histopathological examination was performed by light, scanning electron, andtransmission electron microscopy.Result:Coronary arteriography revealed that3rabbits in the BSA group had various levels ofdilation and narrowing of the left coronary arteries while, histological examination showedthat10rabbits had infiltration of the coronary arteries by inflammatory cells. Incompleteendothelium, breakage of elastic fiber, and intimal thickening was also observed in theBSA group. Granuloma changes, spotty necrosis composed of mononuclear cells wasobserved in the Lung tissue, kidney tissue and liver of BSA group.Ultrastructurally,3rabbits in the BSA group leukocyte migration, shedding of endothelial microparticles fromthe plasma membranes, abscission of endothelial cells, breakage of the internal elasticlamina (IEL), degeneration of smooth muscle cells in the medial membrane were detected.By contrast, the IEL of the NS control group was continuous and of uniform thickness. Conclusion:This rabbit model of coronary arteritis displayed histopathological and ultrastructuralfeatures similar to those of Kawasaki disease in humans. Breakage of the IEL, a key factorin aneurysm formation, was observed in the coronary arteries. Therefore weanling rabbitsmay serve as an experimental model for immune complex vasculitis involving coronaryarteries that mimics Kawasaki disease. Objective:To study the effects and mechanism of simvastatin on pathological damage and therelease of endothelial microparticles in the rabbit model of Kawasaki disease, in order toprovide scientific basis for protecting the endothelial cell to prevent and cure Kawasakidisease.Methods:Experimental groups:30weanling rabbits were randomly and equally divided intomodel group, simvastatin group, saline control group for BSA or normal saline (NS), andadministered the respective treatment by intravenous injection at day1, day14for twocycles.(model group and simvastatin group for BSA; saline control group for NS)The simvastatin group, administered intragastrically with (5mg/kg.bw.d) leadsimvastatin for three weeks after the second injection; and at day7,day14and day21afterthe second injection (ie, acute period, sub-acute phase and recovery phase) blood sampleswere collected.Testing methods:(1) Examination of modeling method:â‘ Histopathological examination of rabbitsmyocardium and coronary organization;â‘¡coronary angiography;(2) ELISA assay foe plasma endothelial nitric oxide synthase (eNOS);(3) Flow cytometry method for the determination plasma endothelial microparticles(EMPs:CD62E+EMPs, CD105+EMPs, CD144+/CD42b-EMPs) expression levels. Result:1. Histological examination showed that10rabbits (10/10) had infiltration of thecoronary arteries by inflammatory cells. Incomplete endothelium, and intimal thickeningwas also observed in the BSA group and heavier than the simvastatin group; complete andsmooth coronary endothelial was observed in saline control group;2. eNOS levels: the expression level in simvastatin group level was significantly (P<0.05)lower than the model group; the simvastatin group compared to the saline control group,P>0.05, the difference was not statistically significance.3. The comparison of plasma EMPs (acute, sub-acute phase and recovery phase)(1)The EMPs expression level: the model group, simvastatin group was significantly(P <0.01)higher than and the saline group;(2)The comparison of model group and simvastatin:â‘ CD62E+EMPs andCD105+EMPs(acute phase, sub-acute phase and recovery phase): the model group wassignificantly (P<0.01) higher than and the simvastatin group;.â‘¡CD144+/CD42b-EMPs:model group was significantly (P=0.001, P<0.01) higher than and the simvastatin groupinthe acute phase; subacute phase (P=0.199) recovery period (P=0.096) higher than thesimvastatin group, but the difference was not statistically significant;4. Pairwise comparison of model group plasma EMPs expression levels:(1) CD62E+EMPs: acute phase was significantly (P<0.05) higher than the sub-acutephase and convalescence.(2) CD105+EMPs: acute phase was significantly (P<0.05) higher the recovery period;(3) CD144+/CD42b-EMPs: recovery period was higher than the acute phase,sub-acute phase, and sub-acute phase was higher than the acute phase, and the differencewas statistically significant. Conclusion:1.Simvastatin can reduce the release of endothelial microparticles and improveendothelial dysfunction, simvastatin can increase the bioavailability of nitric oxide toimprove endothelial function by improving the stability of eNOS expression, eNOS isinvolved in the mechanism of protection, provide the basis for KD coronary endothelialprotection.2.CD144+/CD42b-EMPs sustained increases in convalescent prompted endothelialdamage persists in KD. Three phenotypic EMPs, especially CD144+/CD42b-EMPs isavailable for KD long-term prognosis.