| Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus (DM) and it has become the major cause of end stage renal disease (ESRD). Hyperglycemia and metabolic abnormity, blood dynamic changes,over expression of cytokines and other factors play a role in the development and progression of diabetes nephropathy. Recently, people focus more and more attention on inflammation and im munal factors. A lot of proinflammatory cytokines and chemokines were secreted by the infiltrational inflamematory cells and the intrinsic renal cells, leading to renal des-truction. Taking OLETF rats as our research objects, this is similar as human type 2 diabetes mellitus. Taking Rosiglitazone Maleate Tablets as the treatment drug.We observed the infiltration of macrophages and the expression of NF-κB,MCP-1,IL-12 in OLETF rats'kidney,and discussed their effection on diabetic nephropathy and the possible mechanism. The effection of Rosiglitazone Maleate Tablets on the macroph-ages and the related cytokines was also our reaserch purpose.OLETF rats were our research objects, which were randomly divided into 2 group: the Rosiglitazone group (RT group, n=10) and the OLETF research group (OT group, n=10). LETO rats as the control group (LT group, n=10). Blood glucose,blood lipid changes,24h urine total protein,blood urea nitrogen (BUN),creatinine (Scr) were observed; kidney morphology and ultrastructural changes was observed by light microscopy and electron microscopy;The expression of the cytokine:NF-κB,MCP-1,IL-12 were observed by RT-PCR and immunohistochemistry personally from the genetic and protein levels,CD 68,the surface symbol protein of macrophages, was obsearved by immunohistochemistry,in order to investigate the potential mechenism of the macrophages and related cytokine in diabetic nephropathy and also the effect ion of the Rosiglitazone Maleate Tablets. (1)Compared with the LETO rats,as the weaks grow,the body weight of the OLETF rats increased gradually,also did the 2h postprandial blood glucose, blood lipids(P< 0.05).At 30 weaks, the OLETF rats'urine total protein begin to increase, with the weaks grow,the urine total protein increased gradually(P<0.01).Compared with the OT group,the RZ group'urine total protein decreased (P<0.01).The LETO rats'urine total protein has no greatly change(P>0.05).(2)Light microscopy shows:LT group's glomerulus,glomerular basement membran e,mesangial cells and mesangial matrix,bowman's capsule,renal inerstitium is normal. OT group's glomerulus enlarged, glomerular basement membrane thicked, mesangium was thicken widly, mesangial cells proliferated, mesangial matrix increa sed, bowman's capsule expansed with partly adhesion, also with the glomerulus scl-eraosis, tubular basement membrane thickened, tubular epithelial cells have a change of vacuolization and granular degeneration, lots of fibrous tissue hyperplasiaed and lots of inflammatory cell infiltrated,all of renal pathological changes is similar to the DN (P<0.01). Compared with the OT group, the pathological changes of the RZ group improved significantly (P<0.01).(3) Electron microscope shows:LT group's glomerulus,mesangium areas,foot processes,glomerular basement membrane,renal tubular epithelial cells,mitochondria is normal. OT group's glomerular basement membrane thicked, foot processes fusd, mesangial matrix and mesangial cells increased, a few of densed things deposited; tubular basement membrane thicked irregularlly, mitochon drial cristae ruptured with mitochondria expansed, lysosomes increased with vacuole zation, interstitial tissue expansed. Compared with the OT group, the pathological changes of RZ group were less pronounced.(4) Immunohistochemistry and PCR shows:CD68, NF-κB, MCP-1, IL-12 protein were mainly expressed in renal glomerulus, mildly expressed in renal interstitium,weakly expressed in tubular epithelial cells.Co mpared with LT group, CD68,NF-κB,MCP-1,IL-12 in OT group was higher (P<0.05), OT group was higher than RZ group (P<0.05); There was no or wild expres sion in the LT group. (1)The model of the diabetes nephropathy was made successfully.The OLETF rats' 24h urine total protein and the renal morphological changes are consistent with typical type 2 pathological changes of diabetic kidney.(2) CD68, NF-κB, MCP-1, IL-12 is mainly distributed in the renal glomerulus, may be by local injury and fibration,leads to the injury,fibrous degenerationin and sclerosis of the glomerulus,which plays a role in the pathological development of diabetic nephro-pathy.(3) Rosiglitazone Maleate Tablets may be by restraining CD68, NF-κB, MCP-1, and IL-12's expression to decrease the urine total protein and improve the enlarged glome rulus, thicked glomerular basement membrane and mesangium,the specific mechanis m is worth to research.
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