Abstract | BACKGROUND: 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.
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Authors | Wen-hu Liu, Ni-na Tang, Qi-dong Zhang |
Journal | Chinese medical journal
(Chin Med J (Engl))
Vol. 122
Issue 2
Pg. 199-204
(Jan 20 2009)
ISSN: 2542-5641 [Electronic] China |
PMID | 19187647
(Publication Type: Journal Article)
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Chemical References |
- Benzazepines
- Immunosuppressive Agents
- Platelet-Derived Growth Factor
- Proto-Oncogene Proteins c-sis
- Tissue Inhibitor of Metalloproteinase-1
- Becaplermin
- Matrix Metalloproteinase 9
- Mycophenolic Acid
- benazepril
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Topics |
- Animals
- Becaplermin
- Benzazepines
(therapeutic use)
- Enzyme-Linked Immunosorbent Assay
- Immunohistochemistry
- Immunosuppressive Agents
(therapeutic use)
- Male
- Matrix Metalloproteinase 9
(metabolism)
- Mycophenolic Acid
(analogs & derivatives, therapeutic use)
- Nephrectomy
- Nephritis, Interstitial
(drug therapy, metabolism, pathology)
- Platelet-Derived Growth Factor
(metabolism)
- Proto-Oncogene Proteins c-sis
- Rats
- Rats, Sprague-Dawley
- Tissue Inhibitor of Metalloproteinase-1
(metabolism)
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