The Renal Protective Effect And Mechanisms Of Mycophenolate Mofetil In Diabetic Rats

Objective: To observing the renal protective effect of mycophenolate mofetil(MMF) in diabetic rats and investigating its mechanisms.Methods: SD rats were divided randomly into control group(C) and experimental group after uninephrectomy two weeks later. The experimental group were made diabetic by intraperitoneal injection of streptozotocin, the control group only injected the equivalent buffer. After the diabetic models were successful, they were randomly divided into two groups: diabetic group(D) and diabetic group treated with MMF(M, 20mg·kg-1·d-1). Observed twelve weeks, their blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(Scr), index number of kidney hypertrophy(kidey weight to body weight,KW/BW), creatinine clearance(Ccr) and 24-hour urinary protein (24Upro) were detected. The structure and ultrastructrue of kidney were examined by light microscope and electron microscope. The protein expression of proliferating cell nuclear antigen(PCNA)﹑ macrophages labeled antigen(CD68)﹑ intercellular adhesion molecule-1(ICAM-1) and monocyte chemoattractant protein-1(MCP-1) in kidney tissure were determined by immunohistochemical technique. The mRNA expression of ICAM-1 and MCP-1 were semi-quantitatively determined with reverse transcription-polymerase chain reaction(RT-PCR).Results: Compared with control group, BG﹑KW/BW﹑24Upro﹑BUN﹑Scr and Ccr were significantly increased in diabetic rats (P<0.05 or 0.01); renal pathology showed that the density of glomerular mesangium and the thickness of glomerular basement membrane were significantly enlarged(P<0.01); immunohistochemistry showed the protein expression of PCNA﹑CD68﹑ICAM-1 and MCP-1 were significantly up-regulated(P<0.05 or 0.01); semi-quantitative RT-PCR indicated that there was a increasing mRNA expression of ICAM-1 and MCP-1 in kidney tissure. Except blood glucose, in the MMF treated group the above mentioned parameters were all significantly inhibited(P<0.05 or 0.01).Conclusion: In the diabetic rat model, MMF could decrease urinary protein, ameliorate kidney hypertrophy, inhibite masangial cells﹑mesangium proliferated and decrease the thickness of glomerular basement membrane, thus showing the protective effect in diabetic nephropathy. The mechanisms may be correlated with that it down-regulated the exprssion of PCNA and CD68, decreased the gathering of monocytes/macrophages in kidney tissure and inhibited the over-expression of ICAM-1 and MCP-1.