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COX-2在对乙酰氨基酚致大鼠药物性肝损伤中的作用 被引量:2

Protective effects of COX-2 on acetaminophen-induced liver injury in rats
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摘要 目的探讨COX-2在对乙酰氨基酚致大鼠药物性肝损伤中的作用。方法选择40只SD大鼠随机分成对照组、塞来昔布对照组(A组)、对乙酰氨基酚组(B组)、对乙酰氨基酚+塞来昔布组(C组),每组10只。单次给药,24小时后采集血液测定ALT、AST、ALP、TBA等生化指标,之后处死大鼠,取其肝脏组织行病理学检查,应用免疫组织化学染色方法检测COX-2的表达。结果 B组肝损伤明显,C组肝损伤较B组严重。对照组大鼠肝脏组织未见COX-2的阳性表达;B组有7例COX-2表达呈阳性,阳性率为70.0%;C组仅有1例COX-2表达呈阳性,阳性率为11.1%。结论 COX-2在对乙酰氨基酚所致大鼠急性肝损伤肝组织中表达明显升高,阻断COX-2后,肝损伤加重。COX-2表达增高可能是机体对抗对乙酰氨基酚所致大鼠急性肝损伤的一种保护性机制。 Objective To investigate the role of COX-2 in acetaminophen-induced liver injury in rats. Methods Total of 40 male SD rats were randomly divided into 4 groups: control group, celecoxib treated group (group A), acetaminophen treated group (group B), and acetaminophen combined with celecoxib treated group (group C). Each group was comprised of 10 rats and each rat was given a single dose of appropriate drug. After 24 hours, blood was collected to perform a serum biochemical test of liver function, and liver tissue was harvested for pathological examination and COX-2 expression. Results There was obvious liver damage in group B, and liver injury of group C was aggravated by COX-2 inhibition than group B. There was no expression of COX-2 in hepatic tissue in control group. Positive COX-2 expression were observed in 7 rats of group B, with the rate of 70.0% and only one rat in group C, with the rate of 11.1%. Conclusions Intensity of COX-2 expression increased in group B and liver damage were aggravated after COX-2 blocking-up in the presence of COX-2-selective inhibitors. Induction of COX-2 expression may be a protective mechanism against acute liver injury induced by acetaminophen.
出处 《中国肝脏病杂志(电子版)》 CAS 2011年第4期5-8,共4页 Chinese Journal of Liver Diseases:Electronic Version
基金 广东省自然科学基金(2009B030801142)
关键词 药物性肝损伤 环氧化酶-2 氨基酚类 Drug-induced liver injury Cyclooxygenase-2 Aminophenols
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参考文献14

  • 1易辉,王新,苗继延,杜静平,潘阳林,刘娜,张宇梅,樊代明.选择性环氧合酶-2抑制剂对大鼠酒精性肝损伤的保护作用[J].中华肝脏病杂志,2003,11(11):663-666. 被引量:12
  • 2Rangnekar AS,Fontana RJ.An update on drug induced liver injury. Minerva Gastroenterologica . 2011
  • 3Jeong SW,Jang JY,Lee SH,et al.Increased expression of cyclooxygenase-2is associated with the progression to cirrhosis. Korean Journal of Internal Medicine . 2010
  • 4Yu Y,Gong R,Mu Y,et al.Hepatitis B virus induces a novel inflammation network involving three inflammatory factors,IL-29,IL-8,and cyclooxygenase-2. J Immunol . 2011
  • 5Llorente Izquierdo C,Mayoral R,Flores JM,et al.Transgenic mice expressing cyclooxygenase-2in hepatocytes reveal a minor contribution of this enzyme to chemical hepatocarcinogenesis. American Journal of Pathology . 2011
  • 6Park K,,Williams DP,Naisbitt DJ,et al.Investigation of toxic metabolites during drug development. Toxicology and Applied Pharmacology . 2005
  • 7Bhave VS,Donthamsetty S,Latendresse JR,et al.Secretory phospholipase A2-mediated progression of hepatotoxicity initiated by acetaminophen is exacerbated in the absence of hepatic COX-2. Toxicology and Applied Pharmacology . 2011
  • 8Chitturi S,Farrell G.Drug-induced liver disease. Schiff’s diseases ofthe liver . 2002
  • 9T. A. Ajith,U. Hema,M. S. Aswathy.Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status. Food and Chemical Toxicology . 2007
  • 10Navarro V J,,Senior J R.Drug-related hepatotoxicity. The New England Journal of Medicine . 2006

二级参考文献8

  • 1Ganey PE, Barton YW, Kinser S, et al. Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide. Toxicol Appl Pharmacol, 2001, 174:113-121.
  • 2Vogel C, Boerboom AM, Baechle C, et al. Regulation of prostaglandin endoperoxide H synthase-2 induction by dioxin in rat hepatocytes: possible c-Src-mediated pathway. Carcinogenesis, 2000,21: 2267-2274.
  • 3Denda A, Kitayama W, Murata A, et al. Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.Carcinogenesis, 2002, 23: 245-256.
  • 4Nanji AA, Jokelainen K, Tipoe GL, et al. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther, 2001,299: 638-644.
  • 5Ritter CA, Sperker B, Grube M, et al. Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression. Br J Pharmacol,2002, 137: 1100-1106.
  • 6Henrion-Caude A, Flamant C, Roussey M, et al. Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism. Hepatology, 2002, 36(4 Pt 1):913-917.
  • 7Kanbagli O, Balkan J, Aykac-Toker G, et al. Hepatic mitochondrial prooxidant and antioxidant status in ethanol-induced liver injury in rats. Biol Pharm Bull, 2002, 25: 1482-1484.
  • 8庄丽维,马占军,刘铁夫,梁桃.抗内毒素治疗对肝硬化患者血管活性物质的影响[J].中华肝脏病杂志,2000,8(2):94-95. 被引量:12

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