만성 요독증 쥐에서 안지오텐신 전환효소 억제제와 안지오텐신 수용체 차단제의 신장 보호 효과- 조기 치료와 중등도 신부전 발생 후 치료의 효과 비교 = Renoprotective Effect of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker in Chronic Uremic Rats:Comparison of Early Treatment with Delayed Treatment

다국어 초록 (Multilingual Abstract)

Background:We compared the renoprotective effect of angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) between early treatment and delayed treatment in chronic uremic rats.
Methods:Male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation (sham) and received no treatment (UC), enalapril (E) 100 mg/L, candesartan cilexetil (C) 10 mg/L or combination of E and C in drinking water. Some rats began to be treated from the next day of 5/6 nephrectomy (early group) and the others began from 12 weeks of 5/6 nephrectomy (delayed group). Blood pressure, renal function, proteinuria, histological changes and renal cortical TGFβ1 expression were observed for 24 weeks.
Results:Blood pressure was significantly lower in E, C or E＋C of both early and delayed group than in UC. Particularly blood pressure in E＋C of early group was lower than in E or C. In E, C or E＋C of both early and delayed group, BUN was lower and creatinine clearance was higher compared with UC. Proteinuria was also significantly lower in E, C or E＋C of both early and delayed group compared with UC. In addition, remnant kidney weight in E, C or E＋C of early and delayed group was significantly lower compared with UC, representing less renal hypertrophy. On the histological examination, glomerulosclerosis score, interstitial fibrosis score and the number of infiltrated glomerular macrophage were significantly lower in E, C or E＋C of both early and delayed group compared with UC. Furthermore, renal cortical TGF-β1 expression was also lower in E, C or E＋C of both early and delayed group compared with UC.
Conclusion:ACEi and ARB have renoprotective effect biochemically and histologically even though the treatment was delayed until moderate chronic renal failure had occurred.

국문 초록 (Abstract)

목 적:쥐에서 만성 요독증을 유발하고 안지오텐신 전환효소 억제제와 안지오텐신 수용체 차단제를 조기에 치료한 경우와 중등도 신부전이 발생한 후 치료한 경우 신보호 효과를 비교하고자 하였다.
방 법:Sprague-Dawley 흰쥐의 신장을 5/6 절제하여 만성요독증을 유발하였다. 실험군은 유사 수술을 한 대조군 (sham), 요독증 대조군 (UC), 요독증 쥐에 enalapril maleate (E) 100 mg/L 투여군, candesartan cilexetil (C) 10 mg/L 투여군 및 E＋C 병합 투여군으로 나누고 일부 쥐는 5/6 신절제 다음 날부터 (early군), 일부 쥐는 5/6 신절제 12주 후부터 (delayed군) 약제를 투여하여 24주까지 혈압, 신 기능, 단백뇨, 조직 소견 및 TGF-β1 mRNA 발현을 관찰하였다.
결 과:혈압은 early군과 delayed군 모두 E 또는 C 투여 후 UC군에 비해 유의하게 낮았고, 특히 early군에서는 E＋C 병합 투여 후 E 또는 C 단독 투여에 비해 혈압이 유의하게 낮았다. 신기능은 early군과 delayed군 모두에서 E 또는 C 투여 후 UC군에 비해 유의하게 혈중 요소질소는 낮게, 크레아티닌 청소율은 높게 유지되어 유사한 신보호 효과가 있었다. 24시간 단백뇨는 early군과 delayed군 모두 E 또는 C 투여 후 UC군에 비해 유의하게 낮았고, 특히 early군의 E＋C 병합 투여 후 E 또는 C 단독 투여에 비해 상승 효과가 있었다. 잔여 신장은 UC군에서 심한 비대를 보였으나 early군과 delayed군 모두 E 또는 C 투여 후 UC군에 비해 유의하게 작았다. 신장 조직의 변화에서 early군과 delayed군 모두 E 또는 C 투여 후 UC군에 비해 사구체경화, 간질 섬유화 및 사구체 내 대식세포의 침윤이 유의하게 억제되었다. 또한 UC군에서 증가된 TGF-β1 mRNA 발현도 early군과 delayed군 모두 E 또는 C 투여 후 유의하게 억제되었다.
결 론:만성 요독증 쥐에서 중등도의 신부전으로 진행된 후 안지오텐신 전환효소 억제제 또는 안지오텐신 수용체 차단제를 투여하여도 단백뇨를 감소시키고 신 기능 악화 및 신조직 변화를 억제하는 효과는 현저하였다.

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