VWF In Radioactive Kidney Damnification And The Effect Of Captopril On It

Objective To explore the possible mechanism of glomerulus vWF change and the effect of captopril on plasma and glomerular vWF in radiation renal injury and the mechanism through which captopril affects plasma and glomerular vWF by detecting plasma and glomerular vWF, collagen deposition in glomerular in irradiated rats and radiation renal injury rats which are treated by captopril and analysing the correlation between glomerular vWF and collagen deposition in glomerular.Methods A total of96male SD rats weighing280-300g were randomly divided into three groups:control group (n=20), radiation alone group (n=38), captopril+radiation group (n=38). The latter two groups were subjected to a single-dose of12Gy5MeV electron-ray to the kidneys. The captopril group rats began to receive captopril at the concentration of0.38-0.5mg/ml at24h before irradiation. The blood and urine samples were collected in the radiation alone and captopril+radiation groups at48h,1,2,4,8,16,24weeks after irradiation (six per time in each group). Except for the2weeks after irradiation, kidneys were removed in the two groups at other point in time (six per time in each group). The kidneys, blood and urine samples were collected in the control group at48h,4,24weeks after irradiation (six per time in each group). We detected glomerular vWF by immunohistochemistry, collagen deposition in glomeruli by Sirius Red F3B in saturated carbazotic acid stain and plasma vWF and cystatin C levels by ELISA. Roche biochemical automatic analyzer and roche specific reagent were used to examine urine protein and urine creatinine, and we calculated urine protein clearance by urine protein and urine creatinine. The blood analyzer sysmex XT-1800i was used to determine rat blood leucocyte, erythrocyte, hemoglobin and platelet. The renal morphological feature was observed under light microscope after HE staining.Results LSD-t tests of glomerulus vWF, collagen deposition in glomerular, plasma vWF, plasma cystatin-C and urinary protein clearance in radiation alone group were conducted among each time point. The results of LSD-t tests were as follow: glomerulus vWF increased gradually at16and24weeks after irradiation (t=3.53～6.95,5.71～12.66, P<0.05), collagen deposition in glomerular also gradually increased at8,16and24weeks after irradiation (t=3.03-5.13,3.48-4.68,4.68-9.03, P<0.05), and there was an obvious positive correlation between collagen and vWF (r=0.819, P<0.05); there was an increase in plasma vWF at2,4and16weeks after irradiation (t=3.93～5.03,4.04～5.15,3.48～4.58, P<0.05), plasma cystatin-C (t=5.10～6.17, P<0.05) and urinary protein clearance (t=14.59～16.34, P<0.05) at24weeks after irradiation, and the pathological changes of kidney were mild mesangial proliferation at24weeks after irradiation. In captopril+radiation group, captopril failed to decrease plasma vWF at two weeks after irradiation (F=1.93, P>0.05). Except for that, captopril reduced glomerulus vWF(F=15.60, t=9.82, P<0.05), collagen deposition in glomerular (F=10.24,16.08, t=8.63, P<0.05), plasma vWF (t=3.77, P<0.05; F=4.16, P<0.05), plasma cystatin-C (t=6.68, P<0.05) and urinary protein clearance (t=13.01, P<0.05), and obvious renal pathological changes were not observed In captopril group. Blood routine showed that There was no increase or decrease in blood leucocytes, erythrocytes, hemoglobin and platelets in radiation alone group, control group,and captopril+radiation group at each point in time after irradiation.Conclusions There was a increase in plasma and glomerular vWF, collagen deposition in glomerular in the early radiation renal injury in rats. And there was an obvious positive correlation between collagen and vWF in glomerular. Captopril reduced not only plasma and glomerular vWF but also collagen deposition in glomerular in radiation renal injury rats and effectively protect the kidney. Thus we conclude that the increas in Irradiated glomerular vWF was mainly due to the collagen deposition in glomerular,and endothelial cell damage may also be involved.Captopril might decrease vWF in glomerular by reducing collagen deposition in glomerular and protecting endothelial cell and reduce plasma vWF by protecting endothelial cell.