PMID- 19187647
OWN - NLM
STAT- MEDLINE
DCOM- 20090522
LR  - 20181201
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 122
IP  - 2
DP  - 2009 Jan 20
TI  - Could mycophenolate mofetil combined with benazapril delay tubulointerstitial 
      fibrosis in 5/6 nephrectomized rats?
PG  - 199-204
AB  - BACKGROUND: It was reported that combination of mycophenolate mofetil (MMF) and 
      enalapril could reduce proteinuria, improve renal function, and down-regulate 
      diabetes-induced macrophage recruitment and expression of monocyte chemotactic 
      protein 1 (MCP-1) and transforming growth factor beta (TGF-beta) in diabetic 
      renal tissue. But there are no compelling data available for the combination of 
      MMF and angiotensin converting enzyme inhibitor (ACEI) for suppressing 
      tubulointerstitial fibrosis in chronic kidney diseases. The present study was to 
      disclose the effect of MMF combined with benazapril on delaying 
      tubulointerstitial fibrosis and its possible mechanisms in 5/6 nephrectomized 
      rats. METHODS: Fifty male SD rats underwent 5/6 nephrectomy (5/6 NX) were 
      randomized into the following groups: NX (5/6 nephrectomized rats, distilled 
      water, n = 10), MMF (MMF 20 mg x kg(-1) x d(-1), p.o., n = 10), Ben (benazepril 
      10 mg x kg(-1) x d(-1), p.o., n = 10), MMF/Ben (MMF 20 mg x kg(-1) x d(-1), p.o., 
      and benazapril 10 mg x kg(-1) x d(-1), p.o., n = 10). They were monitored for 
      proteinuria and systolic blood pressure every two weeks. After 8 weeks of 
      treatment, serum creatinine and blood urea nitrogen were assayed and pathological 
      damage to the kidney were evaluated. Renal expression and serum levels of 
      platelet-derived growth factor-BB (PDGF-BB), matrix metalloproteinase-9 (MMP-9), 
      and tissue inhibitor of metaloproteinase-1 (TIMP-1) were detected by 
      immunohistochemistry and ELISA methods. RESULTS: After 8 weeks of treatment, 
      24-hour proteinuria, serum creatinine and blood urea nitrogen were significantly 
      lower in treated groups compared with the untreated rats. MMF and benazepril 
      combination therapy had a greater effect than either drug alone. MMF alone had no 
      effect on systolic blood pressure, but benazapril and MMF/benazapril could 
      significantly reduce blood pressure. Rats that underwent 5/6 nephrectomy had 
      greater tubulointerstitial inflammatory cell infiltration and collagen 
      accumulation than sham-operated rats; all treatments, especially MMF/benazepril, 
      ameliorated these effects. Tubules in 5/6 nephrectomized rats expressed higher 
      levels of PDGF-BB and TIMP-1 and lower MMP-9 compared with sham-operated rats. 
      MMF and benazepril similarly reversed these phenomenons and combination therapy 
      almost completely restored the expression of these cytokines in renal tissue and 
      their plasma concentration. CONCLUSIONS: MMF, especially combined with 
      benazepril, can reduce proteinuria, improve renal function, ameliorate 
      tubulointerstitial fibrosis in 5/6 nephrectomized rats. These effects might be, 
      in part, associated with down-regulation of PDGF-BB and TIMP-1, and MMP-9 
      up-regulation in renal tissues.
FAU - Liu, Wen-hu
AU  - Liu WH
AD  - Department of Nephrology, Affiliated Beijing Friendship Hospital of Capital 
      Medical University, Beijing 100050, China. liuwh0211@yahoo.com.cn
FAU - Tang, Ni-na
AU  - Tang NN
FAU - Zhang, Qi-dong
AU  - Zhang QD
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Benzazepines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 1B56C968OA (Becaplermin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - UDM7Q7QWP8 (benazepril)
SB  - IM
MH  - Animals
MH  - Becaplermin
MH  - Benzazepines/*therapeutic use
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mycophenolic Acid/*analogs & derivatives/therapeutic use
MH  - *Nephrectomy
MH  - Nephritis, Interstitial/*drug therapy/metabolism/pathology
MH  - Platelet-Derived Growth Factor/metabolism
MH  - Proto-Oncogene Proteins c-sis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
EDAT- 2009/02/04 09:00
MHDA- 2009/05/23 09:00
CRDT- 2009/02/04 09:00
PHST- 2009/02/04 09:00 [entrez]
PHST- 2009/02/04 09:00 [pubmed]
PHST- 2009/05/23 09:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2009 Jan 20;122(2):199-204.