併用Phosphodiesterase inhibitor及Angiotensin-converting enzyme inhibitor對慢性腎病之療效
Date Issued
2003
Date
2003
Author(s)
林水龍
DOI
902314B002262
Abstract
We previously reported that pentoxifylline, a phosphodiesterase inhibitor,
attenuates experimental mesangial proliferative glomerulonephritis. In this study, we
hypothesized that pentoxifylline could also attenuate the renal disease progression in
rats with remnant kidney. After 5/6 subtotal nephrectomy, rats developed
progressively elevated proteinuria and plasma creatinine, glomerulosclerosis,
interstitial inflammation and fibrosis, all of which were attenuated by 40 to 60% by
pentoxifylline. However, the elevated blood pressure was not changed by
pentoxifylline. Pentoxifylline reduced the upregulation of monocyte chemoattractant
protein-1 gene by 60% in the cortex of remnant kidney, as well as in a dose-dependent
manner in the albumin- or angiotensin II-stimulated proximal tubular cells. It also
reduced the upregulation of mitogenic and profibrogenic genes by 50%, including
platelet-derived growth factor, fibroblast growth factor-2, transforming growth
factor-1, connective tissue growth factor, types I and III collagen in the cortex of
remnant kidney. Furthermore, pentoxifylline was found to decrease the numbers of
interstitial myofibroblasts by 60% in the cortex of remnant kidney and suppress the
proliferation of cultured interstitial fibroblasts. It also reduced the angiotensin II- or
transforming growth factor-1-induced expression of connective tissue growth factor
gene in cultured fibroblasts and mesangial cells. Combining pentoxifylline with an
angiotensin-converting enzyme inhibitor, cilazapril, almost completely attenuated the
renal disease progression in rats with remnant kidney. In conclusion, pentoxifylline
alone can attenuate the chronic renal disease progression. Its combination with
cilazapril has the potential to prevent the renal disease progression almost completely.
Subjects
subtotal nephrectomy
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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