PMID- 17624267
OWN - NLM
STAT- MEDLINE
DCOM- 20070802
LR  - 20161124
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 120
IP  - 11
DP  - 2007 Jun 5
TI  - Effects of mycophenolate mofetil, valsartan and their combined therapy on 
      preventing podocyte loss in early stage of diabetic nephropathy in rats.
PG  - 988-95
AB  - BACKGROUND: Podocyte has inflammatory role in the development of diabetic 
      nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can 
      suppress macrophage infiltration and reduce renal injury in 
      streptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), 
      another renal protecting agent, can decrease podocyte loss in DN. In this study, 
      we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) 
      and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe 
      and compare the effect of MMF alone and in combination with valsartan, on 
      preventing podocyte loss in streptozotocin (STZ) induced diabetic rats. METHODS: 
      Diabetic model was constructed in uninephrectomized male Wistar rats by single 
      peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats 
      were randomly divided into four groups: diabetes without treatment group (DM), 
      valsartan treated group (DMV), MMF treated group (DMM), and combined therapy 
      group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the 
      end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the 
      ratio of kidney weight/body weight (RWK/B) were measured. The rats were 
      sacrificed for the observation of renal histomorphology through light and 
      electron microscope. Nephrin, desmin and MCP-1 levels were detected by 
      semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used 
      to detect the mRNA levels of nephrin and MCP-1. RESULTS: Compared with group NC, 
      serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher 
      (P < 0.01), and the nephrin mRNA level in DM group was significantly lower (P < 
      0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all 
      higher than that of DM group (P < 0.05) and no significant differences were found 
      among the three treatment groups (P > 0.05). Treatment with MMF, valsartan or 
      their combination could significantly decrease the 24-hour UP and RWK/B, and 
      suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. 
      In diabetic rats, the high expressions of desmin and MCP-1 in kidney were 
      suppressed by valsartan, MMF or their combination. CONCLUSIONS: Podocytes are 
      involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 
      and desmin expression, enhance nephrin expression, and attenuate proteinuria in 
      diabetic rats. The combined therapy of valsartan and MMF did not show any 
      superiority over monotherapies on renal protection. MMF may have renoprotective 
      effect in early stages of diabetic nephropathy through preventing podocytes loss 
      and anti-inflammatory activity.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Nephrology, Second Hospital of Shandong University, Jinan 250033, 
      China.
FAU - Chen, Bing
AU  - Chen B
FAU - Hou, Xiang-hua
AU  - Hou XH
FAU - Guan, Guang-ju
AU  - Guan GJ
FAU - Liu, Gang
AU  - Liu G
FAU - Liu, Hai-ying
AU  - Liu HY
FAU - Li, Xue-gang
AU  - Li XG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Desmin)
RN  - 0 (Membrane Proteins)
RN  - 0 (Tetrazoles)
RN  - 0 (nephrin)
RN  - 80M03YXJ7I (Valsartan)
RN  - HG18B9YRS7 (Valine)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/analysis
MH  - Desmin/analysis
MH  - Diabetic Nephropathies/*drug therapy/pathology
MH  - Drug Therapy, Combination
MH  - Immunohistochemistry
MH  - Male
MH  - Membrane Proteins/analysis
MH  - Mycophenolic Acid/administration & dosage/*analogs & derivatives/therapeutic use
MH  - Podocytes/*drug effects/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Tetrazoles/administration & dosage/*therapeutic use
MH  - Valine/administration & dosage/*analogs & derivatives/therapeutic use
MH  - Valsartan
EDAT- 2007/07/13 09:00
MHDA- 2007/08/03 09:00
CRDT- 2007/07/13 09:00
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2007/08/03 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 2007 Jun 5;120(11):988-95.