Dissertation
Dissertation > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease

The Changes of VEGF and RhoA in Renal Ischemia/Reperfusion in Rats

Author GuoWei
Tutor MengJianZhong
School Taishan Medical College
Course Geriatrics
Keywords Rat Renal ischemia/reperfusion injury (IRI) Vascular endothelial mgrowth factor(VEGF) RhoA/Rho kinase Fasudil
CLC R692
Type Master's thesis
Year 2009
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Objective1.To observe the changes of renal histology and renal function.2.To investigate the serum concentration of Vascular endothelial growth factor (VEGF) and it’s expression of VEGF in renal tissues of male Wistar rat with ischemia/reperfusion injury. 3.To observe the effects of Fasudil on the expression of RhoA and to investigate whether the RhoA/Rho kinase signaling system participate the change of the renal capillary permeability mediated by VEGF.MethodsRat renal I/R model was performed by placing the atraumatic microvascular clamp in both renal artery for 60 minutes. Renal histological changes were observed through light microscope. serum creatinine (Scr) and (BUN) were determined to assess the extent of the injury for renal function; and two-step immunohistochemical methods were applied to study distribution and expression of the RhoA protein in theprocess of renal ischemia/ reperfusion.SerumVEGF were detected at various inter- vals with ELISA;The expression of VEGF in renal tissues was detected by two-step immunoh- istochemical methods.Analysis of variance and dependability were taken on the data.Results1.There were significant pathological changes in renal histology in IR group compared with Con group,the most severity damage showed up at 48h after reperfusion,and significant improvement was found in F group compared with IR group.2.Compared with Con group, the level of Scr、BUN in IR group elevated at 6h of reperfusion (106.33±12.74umol/L、18.41±2.29mol/L), peaked at 48h (201.33±21.52 umol/L、50.42±5.66mol/L) and decreased at 72h (90.17±15.87 umol/L、26.37±3.32mol/L),and there was significant difference between the two groups (P<0.01).The level of Scr、BUN in F group was lower than that of IR group (P<0.01).3. Compared with Con group,renal tubular necrosis score in IR group elevated at 6h of reperfusion (44.3±3.50), peaked at 48h (148.7±5.43)and decreased at 72h (122.5±3.78),and there was significant difference between the two groups (P<0.01).The level of Scr in F group was lower than that of IR group (P<0.01).4.Compared with Con group,the level of serum concentr ation in IR group elevated at 6h of reperfusion (106.33±12.74 umol/L), peaked at 12h (201.33±21.52 umol/L)and decreased at 24h (90.17±15.87umol/L),and there was significant difference between the two groups (P<0.01).The level of serum- concentr-ation in F group was lower than that of IR group (P< 0.01).5.The expression of renal tubule VEGF was gradually upregulated after renal ischemia-reperfusion, peaked at 12h (36.05±4.75%) (P<0.05 vs Con group), and it was distinctly lower in F group than that in IR group at 6h, 12h and 24h (P< 0.05).6.The expression of renal tubule RhoA was gradually upregulated after renal ischemia-reperfusion, peaked at 24h (34.61±6.08%) (P<0.05 vs Con group),and it was distinctly lower in F group than that in IR group at 6h, 12h and 24h(P<0.05).7. In IR group,serum levels VEGF were positively correlated with expression of renal tubule VEGF (r=0.683, P< 0.01).8.In IR group,expression of renal tubule VEGF were positively correlated with expression of serum levels VEGF (r=0.683,P<0.01), Scr (r=0.561,P<0.01), BUN (r=0.552,P<0.01), renal tubular necrosis score(r=0.364,P<0.01).Conclusions:1.Ischemia-reperfusion caused the major injury of nephridial tissue, induced the aggravation of renal function and initiated the renal failure. In renal IRI model,renal function,ren- al tubular necrosis score were all significantly increased after post-reperfusion, and reached its peak in 48h post-reperf-usi on.2.In renal IRI model,serum levels of VEGF was significan- tly increased after post-reperfusion, and reached its peak in different intervals.serum levels VEGF is positively correlated with the expression of tubule VEGF.3.In renal IRI model,Overexpression of tubule VEGF is correlated well with the severity of renal lesions and can reflect the severity of renal lesions.4.It reveals that RhoA/Rho kinase mediated the renal interstitium capillary permeability increase , which was induced by VEGF

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