摘要
目的 研究抗氧化剂N-乙酰半胱氨酸（NAC）对肝脏部分缺血/再灌注（I/R）后肝、肺损伤的保护作用及对Toll样受体2/4（TLR2/4）表达的影响。方法 以BALB/c小鼠复制肝脏部分I/R损伤模型,将小鼠随机分为假手术组、I/R组和NAC干预组（NAC组）,每组10只。于再灌注后1h和3h取门静脉血测定血清肿瘤坏死因子-α（TNF-α）浓度,取眼动脉血测定血浆丙氨酸转氨酶（ALT）水平;同时取受损肝、肺组织行逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（Western blotting）观察TLR2/4表达的变化。结果I/R后受损肝叶和肺组织内出现TLR2/4 mRNA和蛋白的高表达,NAC干预可抑制其表达水平（P〈0.05或P〈0.01）。I/R损伤后血中TNF-α和ALT水平均较假手术组明显升高;NAC干预后各时间点TNF-α和ALT均较I/R组明显下降（P〈0.05或P〈0.01）。结论 小鼠肝部分I/R后,TLR2/4不仅在受损肝组织内有表达,在远隔器官肺内也有表达。NAC可通过调整氧化还原状态,抑制再灌注后TLR2/4的活化和细胞因子TNF-α的表达,从而减轻肝、肺组织的损伤。
Objective To investigate the changes in Toll -like receptor 2/4（TLR2/4） gene expression in liver and lung in ischemia/reperfusion （I/R） injury with or without preconditioning of N -acetyl -L- cysteine （NAC）. Methods BALB/c mice were used in a model of partial hepatic I/R injury and randomly divided into sham -injury control group （SH group）, hepatic I/R group and hepatic I/R with NAC pretreatment group （NAC group）, each n = 10. The level of tumor necrosis factor - α （TNF - α） in portal vein and plasma alanine aminotransferase （ALT） were measured at 1 hour and 3 hours respectively after reperfusion, the expressions of TLR2/4 mRNA and protein in liver and lung were observed with reverse transcription- polymerase chain reaction （RT -PCR ）and Western blotting at the same time points. Results Compared with I/R group, the expressions of TLR2/4 mRNA and protein in liver and lung in NAC group were decreased at same time points （P〈0. 05 or P〈0. 01）. The level of TNF -α in portal vein and plasma ALT increased continually in I/R group at 1 hour and 3 hours after reperfusion compared with SH group, however, they were significantly lowered in the group pretreated by NAC （P 〈0.05 or P 〈0. 01）. Conclusion TLR2/4 is activated in liver and lung in the process of partial hepatic I/R injury. NAC can inhibit the activation of TLR2/4 and the induction of TNF - α resulted from I/R injury via modulating the state of redox process; thus it might mitigate liver and lung injury following partial hepatic I/R in mice.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第7期394-397,共4页
Chinese Critical Care Medicine
基金
国家自然科学基金资助项目（30200272）
