허혈성 재관류 신손상쥐에서 Mycophenolate Mofetil 전처치가 아포프토시스에 의한 세포사와 Mitogen Activated Protein Kinases의 활성화에 미치는 영향 (Effect of Pretreatment of Mycophenolate Mofetil on Apoptotic Cell Death and Map Kinases Activation in Rat Kidneys with Ischemia/Reperfusion Injury)

서지정보

· 발행기관 : 대한신장학회
· 수록지 정보 : Kidney Research and Clinical Practice / 23권 / 3호 / 368 ~ 376페이지
· 저자명 : 안희종, 김완영, 이찬, 김영옥, 양철우, 김용수, 김진, 방병기

초록

목 적:허혈/재관류 신손상 (I/R injury)에 있어 mycophenolate mofetil (MMF)의 전처치가 mitogen activated protein (MAP) kinase의 활성과 아포프토시스에 의한 세포사멸에 미치는 영향을 연구하였다.
방 법:Sprague-Dawley 쥐를 이용하였다. 첫 번 실험은 I/R injury 쥐에서 저용량 및 고용량의 MMF (20 mg/kg과 60 mg/kg)를 일주일 동안 전처치하여 I/R 손상에 대한 효과를 판정하였고, 두 번째 실험은 MMF를 I/R injury 전에 투여하여 MAP kinase의 발현에 미치는 영향을 조사하였다.
결 과:신기능은 sham 군에 비해 I/R injury 군에서 유의하게 저하되었으나 MMF 전처치군에서는 회복하였다. Pro-inflammatory cytokine 및 아포프토시스 관련 mRNA의 발현은 sham 군에 비해 I/R injury 쥐에서 증가한 반면 MMF 전처치군에서는 유의하게 감소하였다. MAP kinase는 MMF 전처치 군에서 I/R injury군에 비하여 유의하게 감소하였다.

영어초록

Background:This study was performed to investigate the effects of pretreatment of mycophenolate mofetil (MMF) on mitogen activated protein (MAP) kinase expression and apoptotic cell death in rat kidneys with ischemia/reperfusion (I/R) injury.
Methods:Three experiments were done separately, In the first experiment, the effect of MMF (20 or 60 mg/kg) on I/R injury was observed. In the second experiment, MAP kinase expression were observed according to the time interval after I/R injury. Finally, the effect of pretreatment of MMF (20 or 60 mg/kg) on I/R injury in terms of apoptotic cell death and MAP kinases were evaluated. We also studied pro-inflammatory cytokines (IL-1 and TNF-alpha) using PCR.
Results:BUN and Serum creatinine level increased in rats with I/R injury but their levels were significantly decreased with MMF Pro-inflammatory cytokines (TNF-α & IL-1) and apoptosis-related gene (caspase-1 and caspase-3 activities) were also significantly decreased as compared with rats with I/R injury. Expressions of MAP kinase were significantly increased in kidneys with I/R injury compared with sham-operated control, but significantly decreased with MMF pretreatment.
Conclusion:Pretreatment of MMF showed a significant decreases of apoptotic cell death, apoptosis-related genes, and MAP kinase expression. This may explain beneficial effect of MMF on subsequent I/R injury.

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