Effect Of Salvianolic Acid B On CD40-CD40L Signal Pathway In Atheros Clerosis Model In Rabbits

ObjectiveExplore the effects of Salvianolic acid B On CD40-CD40L signal pathway inrabbit atherosclerosis model and explore the possible mechanisms ofanti-atherosclerosis.Methods24healthy Japanese big—ear rabbits,a week later adaptive breeding, wererandomly divided into three groups with8rabbits in each group:Black controlgroup、Atherosclerosis Model group、Salvianolic acid B treatment group.Sub-cage rearing, feed volume of120-140g/d.only,free water.Black controlgroup:Normal diet fed at the same time NS fed, giving volume of gastricfeeding by4ml/kg,once a day,continuous12weeks.Atherosclerosis modelgroup:High fat diet feeding,((83.5％ordinary rabbit feed、1.5％cholesterol、10％pig oil、5％egg yolk powder),giving volume of gastric feeding by4ml/kg,oncea day,continuous12weeks.Salvianolic acid B treatment group:TheAtherosclerosis model group with the high-fat feed fed.While giving theSalvianolic acid B8mg·kg-1·d-1,by4ml/kg given volume of gastricfeeding,once a day,continuous12weeks.At the end of the experiment,bloodsamples of the rabbits were collected for biochemistry analysis and aorta wasprepared for morphologic analysis,The expression of CD40L、MMP-9proteinswere detected by immunohistochemical staining and western blot.The changesof sVCAM-1、sICAM-1were tested by ELISA. Results①Pathological morphological observation: the aortic intimal of blank controlgroup was smooth and without atherosclerotic plaque formation;theatherosclerotic model group was uneven and rough,there were manyneedle-like white mastoid processes,some fused into pieces;theabove-mentioned diseases of the Salvianolic acid B group were less. Three-tierstructure of the normal control group were observed clearly through lightmicroscope,vessel wall was smooth and VSMCs arranged regularly;the intimaof the atherosclerotic model group was thicker significantly and irregular foamcells were aggregation,a large number of lipid could be seen at elastic platesand cell gap,smooth muscle cells arranged irregularly;three-tier structure of thevessel wall in the Salvianolic acid B treatment group could be seen clearly,theintima was thick partly,foam cells were less,lipid was deposition rarely,smoothmuscle cells were still arranged neatly.②The influence of Salvianolic acid B on blood lipids and aortic intima andintima-media thickness: compared with the blank group,the AS model groupand Salvianolic acid B group the TC、 TG、 LDL-C content were significantlyhigher (P<0.01),,aortic intima and intima-media thickness were significantlyhigher (P<0.01);compared with AS model group,the TC、TG、LDL-C contentwere significantly lower (P<0.01),,aortic intima and intima-media thickness weresignificantly lower(P<0.01).③The influence on Salvianolic acid B the aorta of CD40L, MMP-9and sVCAM-1,sICAM-1): compared with the blank control group, the AS model group andsalvianolic acid B group rabbit aorta of CD40L,MMP-9expression significantlyhigher (P<0.01), the levels of sVCAM-1, sICAM-1were significantly higher(P<O.01). Compared with the AS model group, salvianolic acid B group ofCD40L、MMP-9expression was significantly decreased (P<0.01), the levels ofsVCAM-1, sICAM-1were significantly lower (P<O.01). Conclusion1、Salvianolic acid B can reduce blood lipids、aortic intima and intima/mediathickness thereby preventing the formation of atherosclerosis.2、Salvianolic acid B can reduce rabbit aorta of CD40L,、MMP-9expressionand the levels of sVCAM-1, sICAM-1.3、The anti-atherosclerosis mechanism of Salvianolic acid B may be relatedto the inhibition of CD40-CD40L signaling pathway.