The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
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The Anti-Inflammatory Effects of Statin in 5/6 Nephrectomized Rats

5/6 신절제 백서에서 Statin의 염증억제 효과에 대한 연구

  • Park, Moo-Yong (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Choi, Soo-Jung (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kim, Jin-Kook (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Hwang, Seung-Duk (Department of Internal Medicine, Soonchunhyang University College of Medicine)
  • 박무용 (순천향대학교 의과대학 내과학교실) ;
  • 최수정 (순천향대학교 의과대학 내과학교실) ;
  • 김진국 (순천향대학교 의과대학 내과학교실) ;
  • 황승덕 (순천향대학교 의과대학 내과학교실)
  • Published : 2011.12.01
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Abstract

Background/Aims: In a previous study, statin therapy reduced proteinuria and ameliorated the progression of chronic kidney disease. However, in patients with chronic renal failure (CRF), the beneficial effect of statin therapy on the preservation of renal function has not been determined. Thus, we determined the effect of rosuvastatin on CRF. Methods: Male Sprague-Dawley rats (6 weeks old) were subjected to 5/6 nephrectomy. Six weeks after the procedure, the rats were divided into control and rosuvastatin-treated groups. Body weight and blood/urine biochemical parameters were measured 6 weeks after 5/6 nephrectomy and 8 weeks after the start of rosuvastatin treatment. Remnant kidneys were harvested at 6 (n = 4) and 14 (n = 8) weeks after 5/6 nephrectomy. Results: During rosuvastatin treatment, changes in body weight and serum total and low-density lipoprotein cholesterol did not differ significantly between the control and rosuvastatin-treated groups. Although serum creatinine and proteinuria increased in both groups, the differences were not significant (p = 0.24 and 0.77, respectively). Immunohistochemical staining, enzyme-linked immunosorbent assays, and western blotting showed that the expression of transforming growth $factor-{\beta}1$ and intracellular adhesion molecule-1 were reduced in the rosuvastatin-treated group. Conclusions: Long-term statin treatment may attenuate the inflammatory process in the progression of renal failure.

목적: Statin이 만성 콩팥병환자에게서 심혈관계 합병증을 감소시키고 단백뇨 감소 효과와 함께 신기능 저하를 지연시키는 작용이 있음은 잘 알려져 있다. 그러나 이미 만성신부전으로 진행된 콩팥병에서 신기능 보호 효과에 대해서는 아직 뚜렷하지 않다. 이에 저자는 만성신부전 쥐 모델에서 statin에 의한 신기능 보호 효과를 알기 위해 연구를 하였다. 방법: 6주 연령의 수컷 Sprague-Dawley (SD) 백서를 대상으로 5/6 신절제술을 시행 후 6주간 관찰하여 만성신부전 모델을 만든 후 대조군과 치료군으로 나누어, 치료군은 rosuvastatin을 8주간 투여하였다. 채혈과 24시간 소변 수집은 신절제술 후 6주와 14주에 각각 시행하였고, 잔여 신장은 6주와 14주에 백서를 희생하여 회수하였다. 결과: 총 12마리 중 6주에 4마리, 14주에 대조군 4마리와 치료군 4마리를 희생하였다. 5/6 신절제 후 6주에 채혈한 검사에서 대조군과 치료군의 평균 크레아티닌은 각각 0.89 ${\pm}$ 0.14 mg/dL, 0.86 ${\pm}$ 0.05 mg/dL (p = 0.55)이었다. 14주에 채혈한 대조군과 치료군의 평균 크레아티닌은 각각 0.97 ${\pm}$ 0.05 mg/dL, 0.94 ${\pm}$ 0.11 mg/dL이었다(p = 0.77). 두 군 사이의 총 콜레스테롤, low density lipoprotein (LDL) 콜레스테롤과 중성 지방은 차이가 없었다. 두 군에서 6주와 14주에 사이의 크레아티닌과 단백뇨의 변화를 비하였을 때 두 군 모두 크레아티닌과 단백뇨가 시간의 경과에 따라 증가하는 추세를 보였으나, 증가 정도를 비교할 때 대조군과 치료군 사이에 유의한 차이는 없었다(p = 0.24, p = 0.77). 신장 조직의 면역조직 화학 염색에서 치료군의 intracellular adhesion molecule-1 (ICAM-1)과 transforming growth factor (TGF)-${\beta}1$ 발현이 감소되어 있었고, 전체 신장 조직의 TGF-${\beta}1$ 농도도 치료군이 유의 하게 낮았다(p = 0.021). 신장 조직에서 측정한 malondialdehyde (MDA) 평균 농도는 치료군이 낮았으나 통계적으로 유의한 차이는 없었다(p = 0.34). 결론: 만성신부전에서 statin 치료는 신부전의 진행에 중요한 항염증 효과를 나타낸다.

Keywords

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