The Function Of Rosiglitazone On The Vascular Remodeling And Endothelial Function In BALB/C Mice With Left Carotid Artery Ligation

Background: Recent studies have shown that rosiglitazone could improve vascular remodeling and endothelial function in some kinds of models by the mechanisms remains unclear. The endothelium can be seen as the first defender to maintain the normal function of vascular, and it is sensitive to the change of haemodynamics. The turbulence of shear stress will change the endothelial function and lead to a facilitation of atheroge- nesis. In the present study, we try to assess the effect of rosiglitazone on the vascular remodeling and the endothelial function in the flow cessation model of male BALB/C mice.Method: 60 male BALB/C mice (12 to 16 weeks'old, 30~40g body weight) were randomized into 4 groups: Operation+Rosiglitazone(OR), Operation+Placebo(O M), Sham-operation+Rosiglitzone(SR) and Sham-operation+Placebo(SM), each group has 15 mice. The blood cessation model was made by ligating the left carotid artery (LCA) at the location of bifurcation with a 6-0 silk. All the mice were given 1 week to recover after the operation. From the 8th day to the 28th day after operation, the 4 groups were administrated with rosiglitazone (20mg/kg) or placebo (methylcellulose, 20mg/kg) by gavage, respectively. On the 29th day, the mice were killed, and the left carotid arteries were isolated and stored at -80℃. HE's photomicrographs were analyzed for morphology. The proteinic expression of cyclophilin A (CyPA) was observed by immunochemistry. The mRNA's amount of ICAM-1 and P-selectin were quantitated by real-time quantitative reverse-transcript PCRs. All replicate data are expressed as mean±SEM. Absolute differences amonggroups were compared using a one-way ANOVA (SNK). Statistical signify- cance was achieved when two-tailed p<0.05. Statistical analyses were carried out using SPSS 13.0 (SPSS Inc., Chicago) for windows.Result:1. 4 weeks after operation, comparing with the sham-operated group, the operation groups achieved significant inward remodeling, including media hypertrophy, neointima hyperplasia, and the decreased lumen diameter of the LCA.2. According to the immunochemistry, CyPA has no difference among the 4 groups.3. The quantizations of ICAM-1's and P-Selectin's mRNA carried out by the real-time quantitative reverse-transcript PCRs have no difference among the four groups (p>0.05).Conclusion:1. Low shear stress can lead to significant inward remodeling of the LCA in BALB/C mice, including the media hypertrophy, neointima hyperplasia, and decreased vascular lumen linked to these changes.2. In this study, rosiglitazone can't improve the LCA's inward remodeling in BALB/C mice with low shear stress, neither the vascular endothelial function in this kind of model.