Lipopolysaccharide/D-Galactosamine에 의해 유도된 급성 간 손상 생쥐모델에서 굴가수분해물의 간 보호 효과

국문 초록 (Abstract)

산화스트레스와 염증은 간 손상의 진행과정에 중요한 인자로 작용한다. 굴가수분해물의 항산화 및 항염증 활성은 지질대사, 혈압 및 혈당, 면역기능의 조절과 같은 다양한 기능에 관여한다. 그러나 급성 간 손상 모델에서 굴가수분해물의 효과를 확인한 연구 결과는 아직 확인된 바 없다. 본 연구는 LPS/D-GalN에 의해 유도된 급성 간 손상 생쥐 모델에서 굴가수분해물의 효과를 확인하기 위해 수행되었다. 실험군은 대조군(생리식염수), LPS/D-GalN 간 손상군, LPS/DGalN과 굴가수분해물(100 mg/kg, 200 mg/kg, 400 mg/kg)의 병합투여군 및 LPS/D-GalN과 silymarin(25 mg/kg) 병합투여군으로 나누었다. 급성 간 손상 모델은 1 μg/kg의 LPS와 400 mg/kg의 D-GalN으로 유도되었다. 먼저 시료의 항산화 및 항염증 활성을 분석한 결과 굴가수분해물은 농도 의존적으로 높은 DPPH 및 ABTS 라디칼 소거 활성을 보였으며, 인간 정상 간세포주(Chang)에서 과산화수소에 의한 세포 내 활성산소의 생성을 유의적으로 감소시켰다. 또한, 굴가수분해물은 농도 의존적으로 높은 COX-2 및 5-LOX 억제능을 보였으며, LPS에 의해 활성화된 생쥐 대식세포주 RAW264.7에서 발현되는 TNF-α, IL-6 및 IL-1α의 염증성 사이토카인의 mRNA 발현률을 감소시켰다. 굴가수분해물 투여는 LPS/D-GalN에 의한 혈청 ALT 및 AST증가를 유의적으로 감소시켰으며, 간 조직의 출혈 및 간세포의 자멸사를 감소시켰다. 또한, 간 균질의 TNF-α, IL-1β 및 IL-6 함량을 감소시켰으며, 감소한 catalase의 활성을 유의적으로 증가시켰다. 이상의 결과로부터 굴가수분해물은 간 보호 효과를 가지는 것으로 판단되며, 급성 간 손상의 예방 및 치료에 도움이 될 수 있는 시료로 활용될 수 있을 것으로 기대된다.

다국어 초록 (Multilingual Abstract)

Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS (1 μg/kg) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1α expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in TNF-α, IL-1β, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.

목차 (Table of Contents)

• ABSTRACT
• 서론
• 재료 및 방법
• 결과 및 고찰
• 요약
• REFERENCES

참고문헌 (Reference)

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