2006Chinese Journal of New Drugs and Clinical RemediesRequires access

Effect of N-acetylcysteine on expression of Toll-like receptor 4 of rats with hepatic ischemia-reperfusion injury

Yan Chungen, N Zhejia

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Abstract

AIM:To explore the role of N-acetylcysteine(NAC)on the expression of Toll-like receptor 4 of rats with hepatic ischemia-reperfusion(I/R)injury.METHODS:Wistar rats were divided into three groups: the pseud-operated control(P)group,I/R group,and I/R+NAC group treated with NAC intra-tail vein adminis- tration with dose of 300 mg·kg~(-1) at 5 min before reperfusion.The concentrations of serum alanine aminotrans- ferase(ALT),aspartate aminotransferase(AST)and plasma lipopolysaccharide(LPS)at various period-point were measured.The expression of TLR4 protein and mRNA of liver tissue were detected with immunohistochem- istry and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:The levels of ALT,AST,and LPS were markedly increased during hepatic ischemia and reperfusion,but they were lower in I/R+NAC group and nearly no alteration in P group.The expression of TLR4 mRNA in I/R group was significantly arised at 3 h after I/R hepatic injury and maintained high level but with no change in I/R+NAC group.The expressions of TLR4 protein were similar between I/R and I/R+NAC group at various time-point.CONCLUSION:LPS and TLR4 play a prominent role in the pathophysiological processes of I/R hepatic injury and NAC can reduce endotoxemia de- rived from gut,inhibit the inflammatory pathway induced by LPS and TLR4,and protect the I/R hepatic injury.

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AIM:To explore the role of N-acetylcysteine(NAC)on the expression of Toll-like receptor 4 of rats with hepatic ischemia-reperfusion(I/R)injury.METHODS:Wistar rats were divided into three groups: the pseud-operated control(P)group,I/R group,and I/R+NAC group treated with NAC intra-tail vein adminis- tration with dose of 300 mg·kg~(-1) at 5 min before reperfusion.The concentrations of serum alanine aminotrans- ferase(ALT),aspartate aminotransferase(AST)and plasma lipopolysaccharide(LPS)at various period-point were measured.The expression of TLR4 protein and mRNA of liver tissue were detected with immunohistochem- istry and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:The levels of ALT,AST,and LPS were markedly increased during hepatic ischemia and reperfusion,but they were lower in I/R+NAC group and nearly no alteration in P group.The expression of TLR4 mRNA in I/R group was significantly arised at 3 h after I/R hepatic injury and maintained high level but with no change in I/R+NAC group.The expressions of TLR4 protein were similar between I/R and I/R+NAC group at various time-point.CONCLUSION:LPS and TLR4 play a prominent role in the pathophysiological processes of I/R hepatic injury and NAC can reduce endotoxemia de- rived from gut,inhibit the inflammatory pathway induced by LPS and TLR4,and protect the I/R hepatic injury.

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Available abstract

AIM:To explore the role of N-acetylcysteine(NAC)on the expression of Toll-like receptor 4 of rats with hepatic ischemia-reperfusion(I/R)injury.METHODS:Wistar rats were divided into three groups: the pseud-operated control(P)group,I/R group,and I/R+NAC group treated with NAC intra-tail vein adminis- tration with dose of 300 mg·kg~(-1) at 5 min before reperfusion.The concentrations of serum alanine aminotrans- ferase(ALT),aspartate aminotransferase(AST)and plasma lipopolysaccharide(LPS)at various period-point were measured.The expression of TLR4 protein and mRNA of liver tissue were detected with immunohistochem- istry and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:The levels of ALT,AST,and LPS were markedly increased during hepatic ischemia and reperfusion,but they were lower in I/R+NAC group and nearly no alteration in P group.The expression of TLR4 mRNA in I/R group was significantly arised at 3 h after I/R hepatic injury and maintained high level but with no change in I/R+NAC group.The expressions of TLR4 protein were similar between I/R and I/R+NAC group at various time-point.CONCLUSION:LPS and TLR4 play a prominent role in the pathophysiological processes of I/R hepatic injury and NAC can reduce endotoxemia de- rived from gut,inhibit the inflammatory pathway induced by LPS and TLR4,and protect the I/R hepatic injury.

Key concepts: TLR4, Reperfusion injury, Lipopolysaccharide, Receptor, Messenger RNA, Ischemia, Chemistry, Toll-like receptor

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