| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 93 === Partial unilateral ureteral obstruction will activate renin-angiotensin system and up-regulates the expression of transforming growth factor-β (TGF-β), tumor necrosis factor (TNF-α), and lead to the accumulation of extracellular cell matrix (ECM) proteins. Protein kinase C (PKC) is a family of serine-threonine kinases that plays a central role in signal transduction and biochemical functions. The aim of this study was to investigate the relationship between angiotensin II generation and protein kinase C activity in partial unilateral obstructed ureter. Furthermore, we studied whether locally produced angiotensin II mediates in TGF-β, and type IV collagen production in renal cortical interstitium, by examining the effects of a protein kinase C inhibitor and angiotensin converting enzyme inhibitor.
Adult male Sprague-Dawley rats were subjected to partial unilateral ureteral obstruction (PUUO) and divided into 3 groups, that is, those without treatment (group O , N=12), treated with angiotensin converting enzyme inhibitor (ACEI) (enalapril) (group E, N= 12) and those with protein kinase C inhibitor (chelerythrine) (group C, N=12). Control animals were sham operated (N=12). Rats were sacrificed at day 7. The relative volume of the tubulointerstitium (Vv) was measured. Proliferating cell nuclear antigen (PCNA), terminal deoxy transferase uridine triphosphate nick end-labeling (TUNEL), and TGF-β, and collagen IV were examined histologically using specific antibodies. Western blot technique was employed for detection of fibronectin and cytosolic or membranous PKCα and PKCβ.
In untreated rats with partial ureteral obstruction, the degree of hydronephrosis was significantly increased than control group, Vv was remarkably expended; collagen IV depositinion in the interstitium and PCNA labeling or TUNEL labeling nuclei were also increased. Increased accumulation of collagen IV and TGF-β expression was blunted by administration of enalapril or chelerythrine. Cytosolic PKCα and PKCβ translocation to membrane were significant and attenuated by ACEI and PKC inhibitor.
This study demonstrated that the renin-angiotensin system has a major role in the pathogenesis of the tubulointerstitial fibrosis of obstructive nephropathy and these data suggested that angiotensin II may active via the PKCα, β pathway.
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