Study Of High Salt And High Fat On The Vascular Intima

Object:In this study,we efforted to construct a new model of artherosclerosis disease in rat which was induced by dietary high salt and high fat intake,and discuss the changes of endangium in this model.At the same we investigated effect of renin- angiotensin- aldosterone system inhibitors and simvastatin on endangium in the modelMethod:1.construction of animal model100 male Wistar rat in 3 weeks old were randomly divided into three groups, which were normal salt group(NS,n=24) fed with diets contained 0.5% NaCl,high salt group(HS,n=24) fed with high salt diets contained 4%NaCl, high salt and fat group (HSF,n=52)fed with high salt and high fat diets contained 4%NaCl and 49%Fat.After 12 weeks,12 rats were chosen randomly in each group and measure the body weight, blood pressure in the carotid artery and K+,Na+,glucose, fat, insulin in blood. then these rats were sacrificed. Pectus aortas were picked up and made into paraffined chip for thichening index of aorta endangium: length of endangium/ tunica media(I/M); The expression of Cx37,Cx40,Cx43,Cx45 and Cx46 in thoracic aorta were detected by immunohistochemistry method. The rest of rats were used for the following experiments2.Intervention of drugsThe rest rats in HSF group were randomly divided into 5 groups again.one group continued to fed with high salt and high fat diets,other 4 groups fed as the same feeder but plus telmisartan(HSF+T,n=8,10mg/kg/d), antisterone(HSF+A,n=8,80mg/kg/d),perindopril(HSF+P,n=8,2mg/kg/d)and Simvastatin(HSF+S,n=8,10mg/kg/d)respectively.All rats were raised until 30 weeks and detected the same index as above.Result:1.change of SBP:At12th or 30th week,SBP level of rats in HSF and HS group was significantly higher than that of age-matched NS group(P<0.05).The data was consistent with our previous results. The result suggested that healthy Wistar rat in 3 weeks old fed high salt or high salt and fat diets could develop into hypertension. Treated with telmisartan, antisterone and perindopril for 18 weeks, SBP of rats in HSF+T group, HSF+P group and HSF+A group significantly lower than that of HSF group and HS group(P<0.05),but not in HSF+S group .The SBP level did not differ among HSF+T, HSF+P, HSF+A group and NS group(P>0.05).Above results demonstrated that RAAS inhibitors could decrease blood pressure level of hypertension model induced by high salt and high salt plus high fat intake.However,after simvastatin was administered for 18 weeks,SBP of rat in HSF+S group could not decrease, compared with that in HSF group and HS group(P>0.05) .But it was higher than that in NC group (P<0.05).the result confirmed Simvastatin had no effect to blood pressure.2.Biochemical Changes in blood:2.1 Blood fat changes:At 12th week,rats in HSF group showed abnormal change in blood fat:level of TG,TC and LDL in rats of HSF group were higher than that of NS group(P<0.05).during 30th week, level of TG and LDL in HSF group was higher than that in NS group. There was no difference in HDL level between that of HSF group and NS group.level of blood fat in HS group had no difference with that in NS group(P>0.05).After drug intervention for 18 week,feeding with telmisartan, antisterone and perindopril,respectively, the level of blood fat in each group did not change obviously. There was no difference between HSF+T group,HSP+P group, HSF+A group and HSF group(P>0.05).level of TG and LDL in these three intervented groups were all higher than NS group(P<0.05).Simvastatin intervention could decreased level of TG and LDL. level of TG and LDL in HSF+S group was lower than that of HSF group(P<0.05);There were no difference in each intervented group,compared with each other(P>0.05)2.2 Changes of fasting blood glucose ,insulin and HOMA-IR index: At 12th week,FBG and HOMA-IR in HSF group were obviously higher that in NS group(P<0.05),butINS level in HSF group did not differ to that in NS group(P>0.05).the above three indexes in HS group did not chang obviously,compared with that of NC group(P>0.05)2.3 Change of Na+,K+ level: Na+,K+ level in each group did not change abnormally in the whole process of experiment.3.Change of endarterium: each group had no sign of arteriosclerosis plaque by HE staining.3.1Intake of high salt or high salt plus high fat could lead to thickening of endarterium:At 12th week,I/M in HSF group and HS group was obviously higher than that in NS group(P<0.05),and the similar tendency showed among HSF group ,HS group and NS group at 30th week.At 30th week, I/M in HSF group was obviously higher than that in HS group (P<0.05)3.2 RAAS inhibitors could slow down the thickening of endarterium: After treated with telmisartan, antisterone and perindopril,respect-ively,I/M in HSF+T group,HSF+P group and HSF+A group were lower than that in HSF group(P<0.05),but they did not differ to that of NS group and HS group(P>0.05)3.3 Simvastatin reduced the thickening of endarterium: after administrated with simvastatin, I/M in HSF+S group was lower than that in HSF group(P<0.05), but was not different with that in HS group and NS group((P>0.05)) 4.The expression of Cx protein in thoracic aorta intima:immunohistochemistry result presented Cx37 protein was expressed abundantly,Cx40 was poor expressed,while Cx43,Cx45 and Cx46 protein were negative.4.1 The level of Cx37 expression were reduced in High-salt group and high-salt plus high-fat group : Display Cx37 expression reduce by comparing IOD values of Cx37-positive regions. HS group and HSF group was significantly lower than NS group at 12 weeks as well as at 30 weeks,P <0.01.4.2 Cx37 expression increased after RAAS inhibitors intervened: Cx37 protein expression was significantly increased in arterial intimal after administrated telmisartan ,perindopril and antisterone respectively for 18 weeks.IOD values of HSF + T group, HSF + P group and HSF + A group was higher than HS group and HSF group, but still lower than NS group, P <0.05.4.3 Cx37 protein expression was increased in arterial intimal after given simvastatin.IOD values of HSF + S group was higher than HS group and HSF group, but still lower than NS group, P <0.05.Conclusion:1.High salt plus high fat could induce normal Wistar rats formed metabolic syndrome (MS) model.2.The model could observe intimal thickening and abnormal expression of Cx37 protein.3.Normal Wistar rats with intake high-salt plus high-fat diets alone can not form atherosclerosis (AS) model.4.RAAS inhibitors and simvastatin could reverse partly changes of endarterium induced by high salt plus high fat.