期刊文献+

Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat 被引量:4

Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat
下载PDF
导出
摘要 AIM: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Z-ValAla-Asp (OMe)-fluoromethyl ketone (ZVAD-fmk) is a cellpermeable irreversible inhibitor of caspase. The purpose of this study was to evaluate the possible effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in the rat.METHODS: Male Sprague-Dawley rats, weighing 250-300 g,were randomized to five groups of five rats each. Group 1 underwent common bile duct ligation and simultaneous treatment with ZVAD-fmk (dissolved in dimethylsulfoxide (DMSO)). Group 2 underwent common bile duct ligation and simultaneous treatment with Z-Phe-Ala-fluoromethyl ketone ( ZFA-fmk, dissolved in DMSO). Group 3 underwent sham operation and simultaneous treatment with the same amount of DMSO. Group 4 underwent sham operation and simultaneous treatment with the same amount of normal saline. Group 5 underwent common bile duct ligation without other manipulation. After three days, liver tissue was harvested for histopathologic analysis and measurements of apoptosis.RESULTS: When compared with sham operation, common bile duct ligation significantly increased hepatocyte apoptosis (P= 0.008) and ductular proliferation (P= 0.007).ZVAD-fmk significantly diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (P = 0.008 and P = 0.007, respectively). ZFA did not show the same effects.CONCLUSION: Hepatocyte apoptosis and ductular proliferation significantly increased after common bile duct ligation. ZVAD-fmk effectively diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas ZFA-fmk did not. AIM:Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Z-Val-Ala-Asp (OMe)-fluoromethyl ketone (ZVAD-fmk) is a cell-permeable irreversible inhibitor of caspase. The purpose of this study was to evaluate the possible effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in the rat. METHODS: Male Sprague-Dawley rats, weighing 250-300 g, were randomized to five groups of five rats each. Group 1 underwent common bile duct ligation and simultaneous treatment with ZVAD-fmk (dissolved in dimethylsulfoxide (DMSO)). Group 2 underwent common bile duct ligation and simultaneous treatment with Z-Phe-Ala-fluoromethyl ketone (ZFA-fmk, dissolved in DMSO). Group 3 underwent sham operation and simultaneous treatment with the same amount of DMSO. Group 4 underwent sham operation and simultaneous treatment with the same amount of normal saline. Group 5 underwent common bile duct ligation without other manipulation. After three days, liver tissue was harvested for histopathologic analysis and measurements of apoptosis. RESULTS: When compared with sham operation, common bile duct ligation significantly increased hepatocyte apoptosis (P= 0.008) and ductular proliferation (P= 0.007). ZVAD-fmk significantly diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (P= 0.008 and P= 0.007, respectively). ZFA did not show the same effects. CONCLUSION: Hepatocyte apoptosis and ductular proliferation significantly increased after common bile duct ligation. ZVAD-fmk effectively diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas ZFA-fmk did not.
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第15期2330-2333,共4页 世界胃肠病学杂志(英文版)
基金 Supported by the grant NSC 89-2314-B-182A-165 from the National Science Council of Taiwan China
关键词 APOPTOSIS Obstructive jaundice ZVAD-fmk ZFA 狂犬病 肝细胞 蛋白酶 ZVAD-fmk 胆管结扎 小鼠 动物实验
  • 相关文献

参考文献31

  • 1Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biology phenomenon with wide-ranging implication in tissue kinetics.Br J Cancer 1972; 26:239-257.
  • 2Allen RT, Hunter WJ Ⅲ, Agrawae DK. Morphological and biochemical characterization and analysis of apoptosis. J Pharmacol Toxical Meth 1997; 37:215-228.
  • 3Cohen GM. Caspases: The executioners of apoptosis. Biochem J 1997; 326:1-16.
  • 4Seiger CP. Anthranoid laxative and colorectal cancer. Trends Pharmacol Sci 1992; 13:229-231.
  • 5Branconnier RJ, Branconnier ME, Walshe TM, McCarthy C,Morse PA. Blocking the Ca(2+)-activated cytotoxic mechanisms of cholinergic neuronal death: a novel treatment strategy for Alzheimer's disease. Psychopharmacol Bull 1992; 28:175-181.
  • 6Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med 1998; 339:1217-1227.
  • 7Miyoshi H, Rust C, Roberts PJ, Burgart LJ, Gores GJ. Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas. Gastroenterology 1999; 117:669-677.
  • 8Patel T, Bronk SF, Gotes GJ. Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. J Clin Invest 1994; 94:2183-2192.
  • 9Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998;101:2790-2799.
  • 10Webster CR, Anwer MS. Cyclic adenosine monophosphate-mediated protection against bile acid-induced apoptosis in cultured rat hepatocyte. Hepatology 1998; 27:1324-1331.

同被引文献18

引证文献4

二级引证文献10

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部