The Relationship Study Of Osteopontin,Adrenomedullin And Tubulointerstitial Injury In Diabetes

Part one The relationship study of osteopontin, adrenomedullin and tubulointerstitial injury in diabetic ratsObjective: To investigate the significance of OPN expression and the level of plasma drenomedullin in tubulointerstitial injury of T1DM animal models : STZ- induced iabetes wistar rats.Methods: Wistar rats were randomly individed into controls(group A) and DM iodels(group B-. C> D, E); Diabetes was induced by a single intraperitoneal injection of TZ(55mg/kg;Sigma,USA) dissolved in 0.4 ml sodium citrate buffer (0.1mol/l,PH4.5).Control its were injected with equivalent doses of sodium citrate buffer; rats were sacrificed at 4^ > 12-. 16 weeks after model-making respectively. The changes of glycemia,renal anctional,urinary albumin excretion rate ( UAER ) ,urinary ai-Microglobulin (ai-MG) ,plasma adrenomedullin,histology (glomerulosclerosis, tubulointerstitial fibrosis, nd ED-1-positive cells as a measure of macrophage infiltration), and expressions of OPN rare evaluated periodically. Analyze the correlation of ADM ^ OPN and tubulointerstitial ijury.Results: Compared with controls,,DM rats showed increases in glycemia, renal function, JAER, urinary ai-MG, plasma adrenomedullin, inflammatory cell infiltration and evelopment of glomerulosclerosis, tubulointerstitial fibrosis, (p<0.01). The expressions f OPN and ED-1 were up-regulated in the DM rats (p<0.01) ; The expressions of OPN lcrease before the up-regulation of ED-1 in tubulointerstitial injury areas of DM rats. The ites of strong OPN expressions were localized to areas of renal injury. Of note, the xpressions of OPN were strongly correlated with the number of ED-1-positive cells, the :vels of urinary ai-MG and plasma adrenomedullin (p<0.01) .Conclusion: Up-regulation of OPN expression may induce macr- -ophage infiltration nd play a role in tubulointerstitial injury associated with diabetic nephropathy. ADM maybe a new index evaluating tubuloi- -nterstitial injury in DM.Part two The relationship study of adrenomedullin and diabetic tubulointerstitial injuryObjective: To study the levels of plasma adrenomedullin in diabetic nephropathy; to investigate the clinical significance of their changes in the development of diabetic nephropathyMethods: We select 10 cases of controls and 42 cases of T2DM patients; patients were divided into 3 groups according to UAER and urinary protein of 24-hour measurement: T2DM without DN(groupA) ,T2DM with DN in initial stage(groupB) and T2DM with DN in clinical stage(groupC).Investigate the levels of plasma adrenomedullin ,serum NO, urinary ai-MG and p>MG; Investigate the relationship of creatinine clearance rate(CCR)^ tubulointerstital injury and the levels of plasma adrenomedullin; Analyze the correlation and function of plasma adrenomedullin and nitric oxide (NO) in initial DN.Results: compared with controls, the levels of plasma ADM rise gradually with the development of DN (p<0.01) . The levels of plasma ADM are positively correlated with urinary ai-MG and pyMQwhich are markers of tubulointerstital injury (p<0.01) . CCR increase in initial DN.ADM and NO both are positively correlated with CCR;ADM are significantly correlated with NO (p<0.01) .Conclusion: The levels of ADM correlate with urinary aj-MG ,which suggest that ADM may be an important compensatory protective factor involving in tubular integrity. In the haemodynamic disorder of initial DN, ADM may act as a vasodilator by the increasing level of NO, promoting the occurrence of glomerular hyperfiltration.