Study Of Protective Effects And Mechanisms Of Ethanol Compounds Extract On Mice With Diabetic Renal Interstitial Fibrosis

AIM:To explore effects of ethanol extract of Schisandra chinensis Rhizoma Chuan xiong Common Oyster Shell(SRC) on nephropathy of diabetic mouse induced by s-treptozotocin (STZ) and to explore its possible mechanisms.METHODS:①Thirty Male C57BL/6 mice were randomly divided into 6 groups: diabetes mellitus (DM) 3 week group, DM6 week group, DM9 week group and the corresponding normal control groups. There were six mice in each DM model group, four in control group. Diabetes was induced by two successive injection of STZ in m-ice using middle dose. serum glucose, right kidney weight,urinary albumin/creatinine ratio, urinary albumin excretion rate(UAER) were measured, Furthermore, the protein expression of E-cadherin andα-smooth muscle actin(α-SMA)in kidney tissues were determined by Western blotting. Fibronectin (FN) expression in kidney tissues were determined by Immunohistochemical method.The morphological changes of renal tissue were observed under microscope.②Twenty-four Male C57BL/6 mice were randomly divided into 3 groups:normal control group, diabetic model group and SRC treated group. Diabetes was induced by injection of STZ in mice. serum glucose, bod-y weight, UAER were measured, Furthermore, the protein expression of E-cadherin,α-smooth muscle actin(α-SMA)and plasminogen activator inhibitor-1(PAI-1) in kidn ey tissues were determined by Western blotting. Fibronectin (FN) andα-SMA expres-sion in kidney tissues were determined by immunohistochemical method.The morph-ological changes of renal tissue were observed under microscope.RESULTS:①Compared with the corresponding normal control groups, blood glucose were significantly increased, weight decreased, right kidney weight and RKBWR significantly increased, and UAER, ACR increasing with the progression of diabetes in DM group. In nice week DM model group we could see:glomerular capillary area increased, mesangial expansion, mesangial matrix proliferation and glomerular basement membrane thickening with PASM stain; mesangial area and tubulointerstitial area shows a large number of mesangial deposition of extracellular matrix with Masson stain and FN immunohistochemistry; Western blot results showed that:As the disease progresses, E-cadherin expression continued to decline,α-SMA expression continued to increase.②Compared with the diabetic model group, SRC could significantly reduce urine albumin excretion rate,right kidney weight(UAER, P<0.01; right kidney weight, P<0.05); increase E-cadherin, reduce a-SMA, PAI-1 expression (P<0.01); inhibit FN and a-SMA expression in tubulointerstitial area; ameliorate tubule extension or atrophy, reduce extracellular matrix accumulate in interstitial.CONCLUSION:Middle dose STZ successive intraperitoneal injection could successfully induced diabetes in C57BL/6 mice; In diabetes-diabetic nephropathy progress, the renal tubular epithelial cells - mesenchymal transdifferentiation and diabetic renal interstitial fibrosis parallel. SRC can ameliorate the renal fibrosis, suppressing epithelial-to-mesenchymal transition(EMT) and the protein expression of PAI-1 is its possible mechanisms.