The Comparison Of The Effects Of Statins On The Mobilization Of Circulation Endothelial Progenitor Cells And The Improvement Of Learning Abilities In Rats Suffered Traumatic Brain Injury

Objective:To tell the differences among statins treatment,we observe the changes of endotheial progenitor cells and learning ability in TBI rats,which received different dosage of Atorvastatin,Simvastatin and Rosuvastatin treatment. In an attempt to hypothesize the mechanism of the"pleiotropic effects"of statins, Provide vivo experimental foundation for using statins in clinic.Methods:The present study used adult Wistar rats(n=88),which were randomly divided into11groups,including Sham group (n=8),TBI+Ns group (n=8), conventional dosage of Atorvaststin group (lmg-kg-1·d-1,n=8),intensive dosage of Atorvastatin group (2mg·kg-1·d-1, n=8),hige dosage of Atorvastatin groups (8mg·kg-1·d-1, n=8), conventional dosage of Simvastatin group (lmg·kg-1·d-1, n=8) intensive dosage of Simvastatin group (2mg·kg-1·d-1, n=8),hige dosage of Simvastatin groups (8mg·kg-1·d-1, n=8), conventional dosage of Rosuvaststin group (0.5mg·kg-1·d-1, n=8),intensive dosage of Rosuvastatin group (1mg·kg-1·d-1, n=8),hige dosage of Rosuvastatin groups (4mg·kg-1·d-1,n=8).In each subgroup, conventional dosage refer to the direction of human dosage level,on which equivalent effective LDL reduction effect is present, intensive dosage is2-fold higher than conventional dosage,while, high dosage is8-fold higer than conventional dosage.We use MODEL01-B hydraulic impact instrument to make TBI models in reference to stereotaxic coordinates of rat brain.rats were oral gavaged with statins according to the dosage and equal-dose saline were treated to NS and Sham groups after TBI. lml daily for21days.Then blood was collected in EDTA tubes from retro-orbital venous plexus by glass capillary.EPCs numbers,WBC numbers,Mono percentage and mNSS were counted on1,4,7,14,21day after TBI,and Morris water maze tests were performed on the day of22to28. Result:1Statins were demonstrated to strikingly improve the mobilization of circulation EPCs.EPCs level raised on4th day and peaked on7th day, then decreased gradully from14th day,which decreased to the baseline on21th day after TBI.Intensive dose of statins were higher than conventional dosage (p<0.05) and high dosage (p<0.05).Simvastatin at2mg/d received the maximun effect on EPCs, which was higher than Atrovastatin2mg (p<0.05) and Rosuvastatin lmg (p<0.05).The mobilization capability of Rosuvastatin was realatively weaker on4-7days,compare with7-14days.2. WBC level was dramatically raised after TBI,and statins prominently declined the inflammatory level compared with Ns (p<0.05).Moreover, statins dose-dependently attenuate the number of WBC, and high dosage group in better than conventional dosage groups (p<0.05) and intensive dosage group (p<0.05)3The effect of statins presented a intriguing phenomenon,that statins decreased the Mono%at first (ld),then raised (4-7d),and after that,decresed again (14-21d) to the baseline.In accordance with anti-inflammtory effect,statins signifigantly declined the precentage of Mono%, Simvastatin at high dosage was stronger than conventional dosage groups (p<0.05) and intensive dosage group (p<0.05)4. In compare with Ns group,the mNss (p<0.05),the Latency time (p<0.05) declined and precent time (p<0.05) were raised gradully. Simvastatin at2mg/d received the better effect on precent time compared with Atorvastatin2mg (p<0.05) and Rosuvastatin1mg (p<0.05),However no statistical differences were found at different dosage (p>0.05)Conclusion:1.Atorvastatin,Simvastatin and Rosuvastatin strikingly improve the mobilization of circulation EPCs and learning ability, declined the inflammtory level and Mono%in TBI rats.2.Simvastatin at2mg/d received the maximun effect on EPCs, and learning ablities, compared with Atrovastatin2mg and Rosuvastatin1mg. 3.Anti-inflammatory effect and Mono%decline effect had no statistical differences in statins.4With dosage ascending,the mobilization of EPCs was increased, however it was declined at a threshold. Statins dose-dependently attenuate the number of WBC and Mono,which lead to descrease in EPCs numbers..5statins dose-dependently attenuate the number of WBC and Mono%。6However, no statistical difference was found in improvement of learning ablities at different dosage. The probable reason was, that the improvement of statins on the function of EPCs took adavatage of that on mobilization.