Research On The Prevention Of Diabetic Nephropathy In The Early Stage Of Diabetes By Statins And Angiotensin Receptor Blockade

Objective: (1) To compare the effect of high concentration glucose and low concentration glucose on the proliferation of mesangial cells and to investigate the inhibiting effects of HMG-CoA reductase inhibitor atorvastatin, simvastatin and angiotensin receptor blockade losartan on the over-proliferation of mesangial cells exposed to the high concentration glucose. (2) To investigate the early nephropathy in the streptozotocin induced diabetic rats in vivo and the treatment effect of simvastatin and losartan on the early diabetic nephropathy in the streptozotocin induced diabetic rats.Methods: (1) The mesangial cells were cultured in the low glucose medium (glucose concentration is 5.6mmol/L) and high glucose medium (glucose concentration is 30mmol/L) treated by different concentration of atorvastatin, simvastatin and losartan. The cell proliferation was determined by the MTT method. (2) The diabetic S-D rats were induced by injection of streptozotocin, and then were randomly classified to the simvastatin treated, losartan treated orcontrol group. Eight weeks after the onset of hyperglycemia, the rats were sacrificed and the ratio of whole kidney to body weight , the structure damage of the kidney, the expression of the connective tissue growth factor, the urinary TGF- 1 excretion and the 24 hours urinary protein were measured.Results: (1) the high concentration glucose induces the over proliferation of mesangial cells and atorvastatin, simvastatin and losartan inhibit the over proliferation in a dose-dependent and time-dependent way. (2) The diabetic control rats showed enlarged kidney/body weight ratio, renal structure damage, increased urinary excretion of TGF- 1 and protein, while simvastatin and losartan prevented these changes.Conclusion: (1) Atorvastatin, simvastatin and losartan can inhibit the over proliferation of mesangial cells induced by the high concentration glucose; (2) Simvastatin and losartan can prevent the development of diabetic nephropathy through inhibition of expression of CTGF and inhibition of secretion of TGF- 1.