Effects Of Atorvastatin On Inflammation And Endothelial Function In Hyperlipidemia Rabbits After Intervention

Objective:To establish hyperlipidemia rabbit model, and to approach the effects of hyperlipidemia and intervention on inflammation and endothelial function in rabbits.In addition,we observed the influence of atorvastatin on improving endothelial function and decreasing inflammation, discussed the possible mechanism of atorvastatin in preventing restenosis,and provided new idea and method for the treatment of restenosis after intervention.Methods:1 Establishing hyperlipidemia rabbit modelChoosing 30 healthy, male, New Zealand white rabbits,the average body weight was 3.0±0.5 Kg. After adaptive feeding for one week, rabbits were randomly divided into two groups: control group (group A,n=15) and the experimental group(group B, n=15) , two groups were given high fat diet until the end of experiment.Every rabbit of the group B was given atorvastatin 2.5mg/Kg/day after three weeks'high fat diet until the end of experiment.After 4 weeks'high fat the model was established.2 Intervention operation.After the model was established,every rabbit was given a general anaesthesia with 1% of pentobarbital sodium according to 0.3 ml/kg. Fixed the rabbit,choosed the left groin, depilated disinfected and covered, cut the skin along the femoral artery, separated subcutaneous tissue,exposed and separated femoral artery completely, blocked the bloodstream,introduced 0.014 guidewire after successful retrograde puncture,withdrew the niddle, introduced balloon introducer which was 1.0 mm in diameter along the guidewire, filled the balloon with isotonic Na chloride through pump,the pressure was 2atm.Then pulled and pushed the balloon, repeated 3 times, injured the vascular endothelium, and then ligated the puncture point with thread, above and underneath the point about 2mm,sutured the skin and subcutaneous tissue. Gived 200 units heparin intraoperation through the ear margin vein to prevent thrombosis. Every rabbit was gived 40,000 units gentamycin per day for one week to prevent infection.3 Index detection3.1 Serum lipidsBefore high fat feed ,4 weeks and 6 weeks after high fat feed, detected triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels, applied enzymic method in automatic biochemistry analyzer.3.2 Inflammation detectionBefore high fat feed, before operation,1 day,1 week and 2 weeks after operation, detected high sensitivity reactive protein (hs-CRP),applied ELISA,The procedure was according to the instructions.3.3 Endothelial function detectionBefore high fat feed,before operation,1 day,1 week and 2 weeks later than operation,detected nitrogen oxide(NO),applied nitrate reductase method,and endothelin (ET),radioimmunoassay,The procedure was according to the instructions.4 Statistical processingAll data was processed with SPSS software.Measurement data was analyzed by M±SD.Interclass difference was compared with t-test, P<0.05 show a significant difference,P<0.01 show an extreme significant difference.Results:1 Result of serum lipidsAfter 4 weeks'high fat feed , the TC, TG and LDL -C significantly rised,established hyperlipemia rabbit model successfully.After 6 weeks'high fat feed , for group A ,the TG, TC, LDL levels rised further more,for group B ,the TG, TC levels rised further more,LDL-C level had no change than before.Compared between two groups,after 6 weeks'high fat feed,the TC,LDL-C levels of group B were lower than A,the TG had no difference.the HDL-C had no significant differences all the time.2 Result of the hs-CRP levelThere was no difference before the intervention; 1 day after intervention, the hs-CRP level of two groups rised significantly,the group A was higher than B; 1 week after intervention, the hs-CRP level was the same as preoperative level;2 week after intervention, the hs-CRP level had no change,compared between two groups,there was no significant difference.3 Result of NOThere was no difference before the intervention; 1 day after intervention, the NO level of two groups decreased,the group A was less than B; 1 week after intervention, the NO level was higher than preoperative level in two groups,the group A was lower than preoperative level, the group B was the same as preoperative level;2 week after intervention, the NO level had no change,compared between two groups,there was no significant difference.4 Result of ETThere was no difference before the intervention; 1 day after intervention, the ET level of two groups rised significantly,the group A was higher than B; 1 week after intervention, the ET level was the same as preoperative level;2 week after intervention, the ET level had no change,compared between two groups,there was no significant difference.Conclusions:1 High fat feed could establish hyperlipemia rabbit model successfully in short term.Hyperlipemia won't cause apparent inflammation and endothelial dysfunction in short term.2 Intervention caused acute inflammation obviously, hs-CRP returned to normal level 1 week after the intervention, atorvastatin can reduce the acute inflammation caused by intervention.3 Intervention damaged the endothelial function, decreased NO synthesis, increased ET release, atorvastatin can significantly improve endothelial function, made endothelial function return to normal level as soon as possible.4 Atorvastatin could reduce inflammation and improve endothelial function,it might prevent restenosis caused by intervention these mechanisms.