脂氧素在对乙酰氨基酚所致急性肝损伤中的保护作用及机制研究  

Role of lipoxin in preventing paracetamol-induced acute hepatic injury and its mechanism

作　　者：李世清[1,2] 杜宗汉[1,2] 周晓晴[1,2] 罗君[1,2] 安启娴[3] 靳斌[4] 

机构地区：[1]川北医学院第二临床学院 [2]南充市中心医院消化内科,四川南充637000 [3]云南省第二人民医院消化内科,云南昆明650032 [4]山东大学临床医学系,山东济南250100

出　　处：《中国生化药物杂志》2015年第2期88-91,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：山东省自然科学基金(Y2008C10)

摘　　要：目的探讨脂氧素A4(lipoxin A4,LXA4)在对乙酰氨基酚所致肝损伤中的保护作用及可能机制。方法 100只雄性新西兰大白兔随机分为空白对照组、对乙酰氨基酚组(PCM组)、N-乙酰半胱胺酸组(NAC组)和脂氧素A4组(LXA4组)4组,每组25只。除空白组兔外给其他3组兔对乙酰氨基酚灌胃24 h后NAC组静脉注射NAC,LXA4组静脉注射LXA4,36 h后,麻醉动物取肝脏组织进行免疫组化及RT-PCR分析并检测肝组织中TNF-α和IL-10的表达,Western blot检测NF-κB p65的表达。结果 PCM组NF-κB p65的表达水平明显高于空白对照组(P<0.01),NAC、LXA4治疗组NF-κB p65的表达显著低于PCM组且具有统计学意义(P<0.01)。对乙酰氨基酚组肝脏组织中TNF-αmRNA水平高于脂氧素A4组和空白对照组(P<0.05)。脂氧素A4组中IL-10mRNA表达水平明显高于对乙酰氨基酚组(P<0.05)。结论脂氧素A4通过抑制对乙酰氨基酚中毒所致急性肝损伤中NF-κB p65的活化,下调促炎因子TNF-α基因的表达,促进抗炎因子IL-10基因的表达,从而控制炎症反应进程,继而发挥其肝脏保护作用。Objective To investigate the potential role of the lipoxin A4 in preventing paracetamol（ PCM）-induced hepatic injury,and reveal its possible related signal path. Methods 100 adult male New Zealand white rabbits were randomly divided into five groups,20 rabbits in each group：Control group; PCM group; NAC group; LXA4 group; LXA4 ＋ NAC group. The rabbits were treated with paracetamol for 36 h by gastric lavage,then given NAC of NAC group,LXA4 of LXA4 group,after 24 h,the rabbits anesthetized were removed liver in which TNF-αand IL-10 were analyzed by immunohistochemistry and RT-PCR method. The expression of NF-κB p65 were detected by Western blot. Results The activation of NF-κB p65 was inhibited by lipoxin A4 in patients of paracetamol-induced hepatic injury,and the expression of NF-κB p65 significantly decreased in LXA4 group compared with PCM group with statistically significant difference（ P〈 0. 01）. What＇s more,the expression of TNF-α and TNF-αmRNA in liver of LXA4 group decreased, conversely, IL-10 mRNA levels increased significantly, and there were statistical differences, respectively（ P〈 0. 01）.Conclusion Lipoxin A4 could control inflammation in paracetamol-induced acute heaptic injury via activation inhibition of NF-κB p65,down regulation of proinflammatory cytokine TNF-α level and up regulation of anti-inflammatory cytokine IL-10,which manifests a protective effect on liver protection.

关 键 词：对乙酰氨基酚 急性肝损伤 脂氧素A4 

分 类 号：R575.3[医药卫生—消化系统]