Seaweed Bromophenol Compounds In Diabetic Rat Kidney Injury Protection Research

Objective:To investigate the effect of two seaweed bromophenol compounds A and B on antioxidant, the expression of CTGF and structuarl changes of renal tissue in diabetic rats.Methods:1. Sixty male Wistar rats were randomly assigned to six groups,10 rats each group respectively:normal control group (NC group); the diabetes group (DM group);compound A low dose group (AL group of 1mg/ml);compound A high dose group (AH group of 2mg/ml);compound B low dose group (BL group of lmg/ml); compound B high dose group(BH group of 2 mg/ml). STZ injection to manufacture the diabetic rats model, after 48 h-72 h, tail blood glucose≥16.7 mmol·L-1 for the successful modeling. Intragastric administration compounds A and B each 0.5 ml/100 g.d.for 12 weeks.2. Evaluation of the general condition and the Visceral Indexes:modeling the observed morphological changes in rats and weight changes, and renal hypertrophy index calculated at the end of the experiment.3. Pathological and ultrastructural study:sacrificing part of the kidney tissue, formalin-fixed, the production of common pathology; to take about 1 mm3 of kidney tissue,using 2.15% glutaraldehyde to dye, made ultra-thin sections to observe by transmission electron microscopy.4. Antioxidant levels Rating:Determination of plasma and renal tissue homogenates of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA).5. Connective tissue growth factor protein expression:Using immunohistochemistry assay to observe connective tissue growth factor (CTGF) protein of renal tissue.Results:1. Compared with NC, the renal hypertrophy index of DM rats and intervention groups were significantly increased (P<0.05); compared with DM rats, the renal hypertrophy index of intervention groups were significant lowed (P<0.05); AH group.2. Pathological and ultrastructural observation:Peritubular Obviousinflammatory cell infiltration, severe tubular vacuolation, glomerular shrinking fibrosis, epithelial cell loss and fragmentation, bureaucratic seen in exfoliated cells in DM group; in drug intervention groups, inflammatory cell infiltration, the tubular vacuolar degeneration reduced, glomerularfibrosis has improved, the efficacy of high dose groups were better than low dose groups. To observe the ultrastructure using electron microscope, basement membrane is uniform and no obvious thickening, only a small amount of foot process effacement in NC group; basement membrane thickening of the DM group, foot process enlargement, destruction, extensive integration in DM group; part of the intervention groups reflect fusion of foot processes, irregular basement membrane thickening, but better than the DM group.3. Antioxidant levels of evaluation:the level of MDA in DM rats were higher than NC, the activities of SOD, GSH-Px were significantly lower than NC. Each intervention groups can significantly reduce the level of MDA and increase SOD and GSH-Px activity in the plasma and renal cortex. 4. CTGF was mainly expressed in the glomerulus, followed by expression in the renal tubules. NC group has lower expression of CTGF, significant increase in the expression of CTGF in the DM group, CTGF expression of each intervention groups were higher than NC group, CTGF expression of AH group was lower than DM group (p<0.05).Conclusion:Seaweed bromophenol compounds A, B, can improve body antioxidant levels of diabetic rats, inhibit expression of CTGF, to improve the pathological changes of the kidney, reduce kidney damage, but the exact mechanism needs further study.