| ObjectiveRenal fibrosis is a common result of modeling caused by various injury such as radiation, trauma, anemia and post-transplanted renal. Up to now, The molecular pathogenetic mechanism of renal fibrosis has not still been revealed. So the present clinical treatment of it is not effective . In the present studies, we used irradiated the renal of Wistar rats with 60Co rays to establish animal model of renal fibrosis . Both the specimen of rats renal fibrosis and post-transplanted fibrosis human kidney was sectioned . Using the mole-biological method to investigated the molecular pathogenetic mechanism of renal fibrosis, In order to make a clue for the clinical treatment of renal fibrosis.MethodAltogether 130 mature specific-pathogen-free male Wistar rats were randomly divided into five groups irradiating the both kidney of the rats with which 10Gy,30Gy,50Gy and 60Gy of single dose of Cobalt 60 rays , 23 rats were unirradiated controls. Kidney function analysis were measured both BUN and Cr . Renal tissues were fixed overnight in 4% paraformaldehyde, routinely processed and embedded in paraffin and 3 to 4 |xm sections were used for H. E stain, Masson stain, Sirius red stain ( under the polarizing microscope). The expression of ot-SMA, ,FN,TGF- 1 and PAI-lwere detected using immuno-his-to-chemical ABC method or in situ hybridization technique. In addition, the renal fibrosis of human transplanted renal were studied to investigate the mRNA level of TGF- 1 and PAI-1 with in situ hybridization.ResultsThe rats were all dead after 2 months post-irradiated in 50Gy and 60Gy groups, after 2 months post-irradiated periods, the death rate of 10Gy and 30Gy groups were 8.0% , 60.9% respectively. It suggested that the high the irradiated dose, the high death rate of the animal and the earlier the rats death point.Microscopic examination found that the changes of rat renals were acute inflammation at initial stages. Such as swelling and atrophy of glomeruli and tubu-li, dilated capillaries ,thrombosis or capillaries collapse, increased of ICE intra-capillaries, there was edema of interstitial and endothelial cells , the cells of macrophages and lymphocytes were composition, the tubular lumen and cavities of glomeruli were narrow , increased of fibers components were found too.The rat renals were progressively changes to renal fibrosis after 1 year in post-irradiated periods of 30Gy group. It was 4 phases; the acute inflammation phase, which occurred within 1 month after irradiation. Hyperfusion and bleeding were found in kidney and capillaries , thrombosis or capillaries collapse, increased of ICE intra- capillaries, thrombosis or capillaries collapse, increased of ICE intra- capillaries. Capillaries proliferation phase: There were dilated capillaries and increased of ICE intra- capillaries, the mesangial and the wall of tubular were thickened and number of cells was added, mainly fibroblasts. The fibers of collagen and selastic were increased, the fibers of lattile were reticular distributed. The renal fibrosis phase; The mesangial and the wall of tubular were thickened greatly, the tubular lumen was narrow especially in the neck of tubul-glomerular and local fibrosis in interstitial was found. The reticular fibers were skeliton like distributed. The glomerular sclerosis phase; the segmental kidney unit were substituted with fibers, the tubular lumen was seriously smaller or disappear , the number of cells were decreased, it can hardly seen selastic and reticular fibers.Using the molecular biology method to investigate tissues of renal fibrosis we can found that there were higher positive rate of -SMA, FN ,TGE- 1 andPAI-1 varied tissue type of the rats kidney. It has significance different internal the every groups and co-related to the irradiated dose and the post-irradiated time.With in situ hybridization technique to detect the expression of TGF- 1 and PAI-1 mRNA in 32 cases of human post-transplanted renal fibrosis we found that there were high positive expression rate in the tissues and... |
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