"Metabolic Memory" Effects On The Progress Of Diabetic Nephropathy

Objective:To explore the effect of "metabolic memory" on progress of diabetic nephropathy,and improve the pathogenesis of DN further more.Methods:Part Ⅰ (invivo Experiment)：choose adult male Wistar rats, divide them into threegroups randomly: Normal control group (NC group, n=15); STZ-induced diabeticnephropathy model group (DM group, n=15); Insulin treated diabetic nephropathy (DIgroup, n=15). NC, DM, DI groups all fed normal diet. The rats of DI group were curedby inject Insulin to make sure the random blood glucose less than11.1mmol/L whenDM modeling successfully for4weeks,and adjust the dose of insulin according to dailycaudal vein blood glucose measurement,total dose of single is6-8IU/D, while DMgroup was given normal saline intraperitoneally every day, observe3groups for8weeks.Then we evaluate blood-fasting sugar、 SCr、 BUN、albumin and cystatin; observe thechanges of renal tissue along with deposition of PAI-1、CTGF by pathology andimmunohistochemical methods.Part II (invitro Experiment): Cells (experiment): divided into four groups:(1) thenormal blood sugar group (NG);(2) high blood sugar group (HG);(3). Turnhyperglycemia hypoglycemia group (HG-NG);(4). High blood sugar group+mannitol(HG+M); Realtime-qPCR method is applied to detect the expression of CTGF andPAI-1.Results:Compared with NC group, kidney hypertrophy index，blood glucose, SCr, BUN inthe DM, DM groups were more significantly increasing. histopathological examinationrevealed DM group’s glomeruli, tubular structure have lesions significantly: glomerularbasement membrane thickening, inflammatory cell infiltration, tubular epithelial cell degeneration, atrophy; renal interstitial fibrotic obviously, nflammatory cell also can beobserved.Compared with the DM group, renal hypertrophy index decreased,blood-fasting sugar, SCr levels decreased significantly and kidney lesions reducerelatively in DI group.Conclusions：1,(invivo Experiment): Although diabetic rats’ blood glucose has been controlled to thenormal range by injecting insulin, the increase of24-hours urine protein has not beensignificantly improved. And the expression of CTGF、PAI-1，renal tissue fibrosisfactors,is still high.2,(invitro Experiment): Although GMC has been cultured from high blood glucose tonormal blood glucose,fibrosis factors CTGF、PAI-1expression levels are not declinesignificantly.3, The results above suggest："metabolic memory" occurred in kidney tissue and celleven blood glucose has been controlled to normal range, and could promote thedevelopment of diabetic nephropathy.