The Effect Of Atorvastin On Mobilization Of Endothelial Progenitor Cells And Renovation Of Remnant Kidney In Rats

Objective: To explore whether atorvastin can mobilize endothelial progenitor cells to remnant kidney and to participate in renovation of 5/6 nephrectomy in rats, and to explore possible mechanisms.Methods: 32 rats were randomly assinged to four groups with 8 animails each proup: sham-operated (control group), subtotal renal ablation (model group), subtotal renal ablation with low does atorvasti(n8mg·kg-1·d-1)(LD), subtotal renal ablation with high does atorvastin (HD). After 8 weeks, total mononuclear cell (MNCs) were isolation from peripheral blood with ficoll density gradient centrifugation, and then the cells were plated on fibronetin-coated culture dishes. After 7 day cultured, the attached cell morphology were observed, and cell number were counted. Flow cytometry was used to detect the expression of CD34, CD133 and KDR of the cultured cells, and immunofluorescence was performed to display the character of endocytosing UEA-1 and combining acLDL, and the capacity of the cells'proliferation, adhesion were further ovserved. CD31,CD34 immunohistochemistry was used for detecting glomerular capillary density and homing cells. RT-PC-R was used for detecting the expression of TGFβmRNA, collegen typeⅣmRNA, VEGF mRNA, ET mRNA and eNOS mRNA. HE and PAS Sirius red staining of collagen were used for detecting the renal pathological changes. Lever of Scr, BUN, CUP, TCHO, TG, LDL, AST, ALT and CK were detected.Results: The cells could take up DiI-acLDL, and bind to FITC-UEA-1, showed double positive fluorescence under LSCM. Cultured EPCs at the passage 1 were positive for CD133, CD34 and VEGFR-2 (4.14%, 79.42% and 55.7% respectively), After treatment of atorvastin, the capacity of the cells'proliferation and adhesion were promoted significantly (P<0.05), and the number of EPCs was increased significantly (P<0.05). The number of CD34 cells in nephridial tissue and the density of glomerulus CAP endothelial cell were increased significantly (P<0.05), the expression of mRNA of VEGF and eNOS in nephridial tissue were raised significantly (P<0.05), the expression of mRNA of ET-1, TGF-βand IV collagen were falled significantly (P<0.05, P<0.01). Inflammatory cells infiltrated, mesangial cells proliferated, mesangial matrix deposited, renal interstitial fibrosis and glomerulosclerosis were reduced significantly (P<0.05 ,P<0.01). The urinary protein, Scr and BUN of atorvastin group were reduced significantly (P<0.05). There was no significant difference between groups about TCHO, TG,, LDL, AST, ALT and CK.Conclusion: Atorvastatin degraded Scr, BUN, CUP with does-dependent, without anything of lipid levels. Atorvastatin increase peripheral blood EPCs, improved EPCs proliferation, and adhesion with does-dependent, and mobilized EPCs to remnant kidney to participant in vascular repairing, promoting promote angiogenesis. Atorvastatin lightened remnant kidney's inflammatory cell infiltration, mesenterium hyperplasia, mesangial matrix deposition, basement membrane thickening, collagen fibers deposition, glomerular sclerosis and renal interstitial fibrosis.