마우스에서 사이클로스포린 유발성 급성 신장 손상에 대한 Green Tea Polyphenol의 항단백뇨 효과 = The Antiproteinuric Effects of Green Tea Polyphenol on Cyclosporine A-Induced Acute Renal Injury in Mice

다국어 초록 (Multilingual Abstract)

Background : It has been reported that there is association between cyclosporine (CsA) nephrotoxicity and proteinuria. The aim of this study was to investigate the anti-proteinuric effects of green tea polyphenol (GTP) on CsA-induced acute renal injury in mice.
Methods : The mice (n=20) were divided into 4 groups (n=5/group); group 1 (control group) mice were intraperitoneally (IP) injected 0.9% saline, group 2 (CsA group) mice were IP injected CsA 50 mg/kg, group 3 (iNOS inhibitor group) mice were given in addition NG-nitro-L-arginine-methyl ester (L-NAME) 12 mmol/L by subcutaneous injection. Group 4 (GTP group) mice were given CsA by IP injection and GTP 100 mg/kg by subcutaneous injection.
Results : Urine protein significantly increased in group 2 (28.6±11.1 g/kg/day) compared to group 1 (9.1±5.5 g/kg/day, p<0.01) and significantly decreased in group 4 (11.2±8.8 g/kg/day, p<0.01) compared to group 2. Renal tissue malondialdehyde level of group 2 significantly increased compared to group 1 and significantly decreased in GTP group (p<0.01).
Conclusion : This study proves that proteinuria of the CsA induced nephrotoxicity is associated with lipid peroxidation and nitric oxide production. GTP treatment has meaningful antiproteinuric effects through antioxidative effect in the kidney from CsA-induced acute renal injury.

국문 초록 (Abstract)

배 경 : 사이클로스포린은 신장 이식 후 가장 많이 사용하는 면역억제제이지만 신독성이 중요한 부작용 중의 하나이다. 항산화제로 알려진 green tea polyphenol (GTP)이 사이클로스포린 신독성에 의한 항단백뇨 효과가 있는지를 알아보고자 하였다.
방 법 : 마우스 (mice 20-25 g, 20마리)를 4 군으로 분류하였는데 1 군은 대조군 (5마리)으로 생리식염수를 복강에 투여한 군, 2군은 사이클로스포린 군 (5마리)으로 사이클로스포린 50 mg/kg를 복강 내로 투여한 군, 3군은 inducible nitric oxide synthase (iNOS) 억제제 병합 투여군 (5 마리)으로 사이클로스포린 50 mg/kg과 같이 NG-nitro-L-arginine -methyl ester (L-NAME) 12 mmol/L을 피하로 투여하였다. 4군은 GTP 병합 투여군 (5 마리)으로 사이클로스포린 50 mg/kg을 복강으로 투여한 후 GTP는 100 mg/kg을 피하로 투여하였다.
결 과 : 소변 단백 양은 대조군 (9.1±5.5 g/kg/day)에 비하여 2군에서 의의있게 상승하였으며 (28.6±11.1 g/kg/day), 3군 (18.5±9.4 g/kg/day)에서와 4군 (11.2±8.8 g/kg/day)에서 2 군에 비하여 의의있게 감소하였다. 신장 조직의 malondialdehyde 농도는 2 군에는 대조군에 비하여 의의있게 상승하였으며, 3군과 4군에서 2군에 비하여 의의있게 감소하였다. 항산화 효소 활성도 분석에서 2군의 항산화 효소 활성도가 대조군에 비하여 의의있게 낮았으며, 4군에서 의의있게 회복됨을 관찰하였다.
결 론 : GTP를 사이클로스포린과 병용투여 하였을 때 항산화 효소의 활성도가 회복되고 산소 유리기를 제거하며 지질 과산화를 차단하여 사이클로스포린의 급성 신장 손상에 대한 단백뇨가 감소하였다.

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