Renal Protective Mechanism Of Losartan And Astragalus Membranaceus For Diabetic Nephropathy

Objective: To observe the protective effect of Losartan and Astragalus Membranace on the kidney of diabetic rats, and to study their possible mechanisms. Methods: Fifty adult male SD rats were divided randomly into five groups:normal contral group, diabetic untreated group, diabetic group treated orally with Losartan(lOmg/kgld), diabetic group treated orally with Astragalus Membranaceus(3glkg/d), diabetic group treated orally with Losartan(lOmg/kgld) and Astragalus Membranaceus(3glkgld). The diabetic rats were induced by a single intraperitoneal injection of streptozotocin. At end of 12 week, the rats of each group were sacrificed. Plasma glucose, glycosylated hemoglobin(HbAi), urinary albumin excretion(UAE), urinary P 2-MG excretion, creatinine clearance(Ccr) were determined. Nitric oxide(NO) and endothelin-1(ET-1) level in plasma,urinary and renal tissue was measured. Serum and urinary transforming growth factor-beta 1 (TGF- 13 i) concentration were measured. The average volume of glomeruler was assessed by optical microscope. The average thickness of glomerular basement membrane was measured by electron microscope. Results: Plasma glucose , 1-IbA1, UAE, urinary f3 2-MG excretion, Ccr, urinary and renal tissue NO, urinary and renal tissue ET- 1, urinary TGF- f3 , average volume of glomeruler and average thickness of glomerular basement membrane in diabetic rats were significantly greater than that of normal contra! rats, but NO, ET-l and TGF- 13 in blood did not change. In the diabetic treated rats, UAE, urinary 173 2-MG excretion, Ccr, urinary and renal tissue NO, urinary and renal tissue ET-1 , urinary TGF- 13 , average volume of glomeruler, average thickness of glomerular basement membrane decreased obviously as compared with diabetic untreated rats. Losartan was superior to Astragalus Membranace in reduction UAE, urinary 173 2-MG excretion and the average thickness of glomerular basement membrane. These effects were enhanced when Losartan was combined with Astragalus Membranace. Plasma glucose and HbAt in the diabetic treated rats remained same level as compared with diabetic untreated rats. Conclusion: (1): At end of 12 week, there was marked injury of renal structure and function in STZ-induced diabetic rats. (2): Losartan or Astragalus Membranace had not valid effect on the high glucose in STZ-induced diabetic rats. (3): NO, ET and TGF- 13 which produced in kidney may be important factors in the pathogeneses of diabetic nephropathy. (4): Losartan or Astragalus Membranace could reduce the amount of renal NO, ET and TGF- 13 t, and reverse the injury of renal structure and function in STZ-induced diabetic rats. Losartan was superior to Astragalus Membranace in reduction UAE, urinary P 2-MG excretion and the average thickness of glomerular basement membrane. The protective effects were enhanced when Losartan was combined with Astragalus Membranace.