Tendency Of Microvescular Injury And Expression Of Molecules Correlated With This Lesion In Tubulointerstitial Fibrosis In The Yang Rats With Unilateral Ureteral Obstruction

Objective: To investigate the expressing tide and potential pothogenic role of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF) in microvascular injury on early stage tubulointerstitial lesions in young rats with Unilateral Ureteral Obstruction (UUO). Meanwhile, to evaluate the interfering effects with angiotensin coverting enzyme inhibitor(ACEI) Benazepril and angiotensinⅡtype 1 recepter angonist(ARB) Losartan.Methods: 96 young male Wistar rats at the age of 2-3 weeks were randomly divided into 3 groups, the control group (n=32),UUO untreated group(n=32),UUO treated group with ACEI and ARB (n=32). At the time points that treated for 1,2,3,4 weeks, eight rats were sacrificed in each group and the kidneys were obtained to evaluate the renal tissue morphologic changes through HE staining. At the same time, we detected and evaluated the protein expression of TSP-1, VEGF and CD34 in tubulointerstitial areas by immunohistochemical ways, as well as the effect of treatment. All the data were analyzed by statistics software SPSS13.0.Results:①Our results showed renal tissue normal in control group. And in UUO untreated group, we observed some significant morphologic changes in tubulointerstitial areas, that include the interstitial edema and the distal tubular dilation at 1st week after UUO. It was showed obviously at week 2, such as more dilated tubuli; generous inflammatory cells which were infiltrated into renal tissue especially in tubulointerstitial regions; foam degenerated tubuler cells, thicken and breaked tubular basement membrane and broadened tubulointerstitial area. With the experimental session continuing ,pathological changes in tubulointerstitial region were becoming more and more serious in untreated group after UUO. Compared with control group,there were significant different in each time points (weeks 1,2,3 and 4). The extent of tubulointerstitial pathological changes in treated group is more alleviative than the untreated group(P<0.05), but still more serious than the control group(P<0.01).②Immunohistochemical staining indicated that in control group CD34 was expressed in the peritubular capillary epiothelial cells. Semi-quantitative value of CD34 expression was, control group: 2.59±0.72,2.89±0.64,2.44±0.44,2.82±0.51;model untreated group:2.12±0.31,1.74±0.16,1.43±1.19,1.09±0.15;treated group:2.78±0.28,2.37±0.38,2.09±0.28,1.71±0.19 at time point of weeks 1, 2,3 and 4 respectively. The decrease of this expression was remarkable in the untreated group (P<0.01), and was moderate in the treated group (P<0.05) in the time-course experiment. TSP-1 proteins were expressed in the wall of Bowman's capsule and VEGF was expressed in the tubular epithelial cells as well as podocytes. Semi-quantitative value of the expression of VEGF was, control group:2.97±0.853.21±0.57,3.11±0.76,3.04±0.55;model untreated group:2.52±0.91,1.76±0.66,1.39±0.71,1.05±0.69;treated group:2.69±0.94,2.46±0.45,2.21±0.40,2.00±0.61 at weeks 1, 2, 3 and 4 respectively. Compared with control group, the expression of VEGF changed moderately (P>0.05) in model group at 1st week, but decreased remarkably at week 2, 3, 4 (P<0.01). However, this decrease was not significant in the treated group (P>0.05). The expression of TSP-1 was mainly located in the Bowman's capsule, mesangial area, glomergular capillary loops and tubulointerstitial region. Semi-quantitative value of TSP-1 was, control group:1.86±0.30,1.81±0.26,1.81±0.18,1.86±0.23;model untreated group:2.02±0.27,3.46±0.28,2.84±0.42,2.93±0.25;treated group:2.19±0.19,3.06±0.27,2.60±0.27,2.69±0.22 at week 1, 2, 3 and 4 respectively. As time going on, this espression was increased significantly in model untreated group (P<0.01). The peak time is the second week and the increase rate is slow at the 3rd and 4th week. All the marking protein expressions are weaker in treated group.Conclusion: Our results have shown that peritubular capillary lesions were observed in tubulointerstitial fibrosis in young UUO rats, and the abnormal expression of VEGF and TSP-1 proteins may participate in this lesion. The interfering effects of ACEI and ARB could ameliorate tubulointerstitial fibrosis by regulating the expression of VEGF and TSP-1 in obstructive renal tissues.