Effect of Cyclooxygenase-2 on Hepatocellular Injury in Rats with Sepsis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

L I B in , L I Yumin , L I X un , Z HOU Wence , Z HU X i aol iang , H E Mingy an

Department of General S urgery , The Fi rst Hos pi tal , L anz hou Uni versi t y , L anz hou 730000 , China;

Corresponding author：

Keywords：

Sep sis ，Cyclooxygenase-2 ，NS398 ，Hepatic injury

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【Abstract】Objective To study the expression of cyclooxygenase-2 (COX-2) in hepatic inflammatory reaction of rats with sepsis, and to explore a new way of protecting hepatic cell. Methods Fifty-four Wistar rats were randomly divided into 3 groups: sham operation group, sepsis group and NS398 group. All rats were subjected to cecal ligation and puncture (CLP) or sham operation. RT-PCR was used to determine COX-2 mRNA expression, serum IL-6, TNF-α and IL-10 were determined by ELISA; and ALT and AST and liver pathological changes were determined in 3 groups and at different times (3, 6, 12 and 24 h) respectively. Results ①The expression of COX-2 mRNA of hepatic tissue was low in sham operation group. It obviously enhanced after CLP at 3 h and peaked at 6 h. High expressions were showed at 12 and 24 h. In NS398 group, it was lower than that of sepsis group at the same time, but higher than that of sham operation group. ②Serum ALT, AST and IL-6, TNF-α were increased in sepsis group than those of sham operation and NS398 group (P＜0.05)； Serum IL-10 was higher in NS398 group than that of sham operation and sepsis group (P＜0.05). ③Hepatic pathological injury extenuate after injected with NS398. Conclusion COX-2 may play an important role in hepatic injury with sepsis.

Citation： L I B in,L I Yumin,L I X un,Z HOU Wence,Z HU X i aol iang,H E Mingy an. Effect of Cyclooxygenase-2 on Hepatocellular Injury in Rats with Sepsis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(4): 266-270. doi: Copy

1.
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3.	Ikezoe T, Yang Y, Heber D, et al. PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock [J]. Mol Pharmacol， 2003; 64(6)∶1521.
4.	O’Reilly M, Newcomb DE, Remick D. Endotoxin, sepsis, and the primrose path [J]. Shock， 1999; 12(6)∶411.
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6.	Flammand FJ, Sibbald WJ, Girotti MJ, et al. Pentoxifylline does not prevent microvascular injury in normotensive, septic rats [J]. Crit Care Med， 1995; 23(1)∶119.
7.	严文伟, 周总光, 陈友琴, 等. 急性水肿性胰腺炎大鼠胰腺微血流变化和环氧合酶-2的表达 [J]. 中华肝胆外科杂志, 2004； 10（4）∶252.
8.	张馨，余卫平. 内毒素损伤肝脏机制的研究进展 [J]. 国外医学·消化系疾病分册, 2002； 22（3）∶163.
9.	Kumagai T, Kawamoto Y, Nakamura Y, et al. 4-hydroxy-2-nonenal, the end product of lipid peroxidation, is a specific inducer of cyclooxygenase-2 gene expression [J]. Biochem Biophys Res Commun， 2000; 273(2)∶437.
10.	Keller SA, Paxian M, Lee SM, et al. Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis [J]. J Surg Res， 2005; 124(1)∶126.
11.	李磊，王兴鹏. 脓毒症的发病机制及其治疗策略新认识 [J]. 国外医学·生理、病理科学与临床分册, 2003； 23(6)∶650.
12.	Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle [J]. Am J Physiol Regul Integr Comp Physiol， 2002; 283(3)∶R698.
13.	Wang P, Li N, Li JS, et al. The role of endotoxin, TNF-alpha, and IL-6 in inducing the state of growth hormone insensitivity [J]. World J Gastroenterol， 2002; 8(3)∶531.
14.	Remick DG, Call DR, Ebong SJ, et al. Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sepsis mortality [J]. Crit Care Med， 2001; 29(3)∶473.
15.	程南生. 脓毒症与感染性休克的免疫治疗 [J]. 中国普外基础与临床杂志, 2004； 11(3)∶276.
16.	Berg DJ, Zhang J, Lauricella DM, et al. IL-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production [J]. J Immunol， 2001; 166(4)∶2674.
17.	Strong VE, Mackrell PJ, Concannon EM, et al. Blocking prostaglandin E2 after trauma attenuates pro-inflammatory cytokines and improves survival [J]. Shock， 2000; 14(3)∶374.
18.	Callejas NA, Fernández-Martínez A, Castrillo A, et al. Selective inhibitors of cyclooxygenase-2 delay the activation of nuclear factor kappa B and attenuate the expression of inflammatory genes in murine macrophages treated with lipopolysaccharide [J]. Mol Pharmacol， 2003; 63(3)∶671.
19.	林洪远, 盛志勇. 脓毒症免疫调理治疗的新思路 [J]. 中国危重病急救医学, 2004； 16（2）∶67.
20.	蒋力生，陈鹏. 脓毒症与内毒素血症的治疗现状与展望 [J]. 中国普外基础与临床杂志, 2004； 11(6)∶551.
21.	Takeeda M, Yamato M, Kato S, et al. Cyclooxygenase iso-zymes involved in adaptive functional responses in rat stomach after barrier disruption [J]. J Pharmacol Exp Ther， 2003; 307(2)∶713.

1.
2. 20 　 Osterberg J, Ljungdahl M, Haglund U. Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis [ J ] . Shock ， 2006; 25(2) ∶ 147.
3. 　Ikezoe T, Yang Y, Heber D, et al. PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock [J]. Mol Pharmacol， 2003; 64(6)∶1521.
4. 　O’Reilly M, Newcomb DE, Remick D. Endotoxin, sepsis, and the primrose path [J]. Shock， 1999; 12(6)∶411.
5. 　邵阳, 王翔. 脓毒血症的治疗进展 [J]. 医学综述, 2002； 8(4)∶244.
6. 　Flammand FJ, Sibbald WJ, Girotti MJ, et al. Pentoxifylline does not prevent microvascular injury in normotensive, septic rats [J]. Crit Care Med， 1995; 23(1)∶119.
7. 　严文伟, 周总光, 陈友琴, 等. 急性水肿性胰腺炎大鼠胰腺微血流变化和环氧合酶-2的表达 [J]. 中华肝胆外科杂志, 2004； 10（4）∶252.
8. 　张馨，余卫平. 内毒素损伤肝脏机制的研究进展 [J]. 国外医学·消化系疾病分册, 2002； 22（3）∶163.
9. 　Kumagai T, Kawamoto Y, Nakamura Y, et al. 4-hydroxy-2-nonenal, the end product of lipid peroxidation, is a specific inducer of cyclooxygenase-2 gene expression [J]. Biochem Biophys Res Commun， 2000; 273(2)∶437.
10. 　Keller SA, Paxian M, Lee SM, et al. Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis [J]. J Surg Res， 2005; 124(1)∶126.
11. 　李磊，王兴鹏. 脓毒症的发病机制及其治疗策略新认识 [J]. 国外医学·生理、病理科学与临床分册, 2003； 23(6)∶650.
12. 　Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle [J]. Am J Physiol Regul Integr Comp Physiol， 2002; 283(3)∶R698.
13. 　Wang P, Li N, Li JS, et al. The role of endotoxin, TNF-alpha, and IL-6 in inducing the state of growth hormone insensitivity [J]. World J Gastroenterol， 2002; 8(3)∶531.
14. 　Remick DG, Call DR, Ebong SJ, et al. Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sepsis mortality [J]. Crit Care Med， 2001; 29(3)∶473.
15. 　程南生. 脓毒症与感染性休克的免疫治疗 [J]. 中国普外基础与临床杂志, 2004； 11(3)∶276.
16. 　Berg DJ, Zhang J, Lauricella DM, et al. IL-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production [J]. J Immunol， 2001; 166(4)∶2674.
17. 　Strong VE, Mackrell PJ, Concannon EM, et al. Blocking prostaglandin E2 after trauma attenuates pro-inflammatory cytokines and improves survival [J]. Shock， 2000; 14(3)∶374.
18. 　Callejas NA, Fernández-Martínez A, Castrillo A, et al. Selective inhibitors of cyclooxygenase-2 delay the activation of nuclear factor kappa B and attenuate the expression of inflammatory genes in murine macrophages treated with lipopolysaccharide [J]. Mol Pharmacol， 2003; 63(3)∶671.
19. 　林洪远, 盛志勇. 脓毒症免疫调理治疗的新思路 [J]. 中国危重病急救医学, 2004； 16（2）∶67.
20. 　蒋力生，陈鹏. 脓毒症与内毒素血症的治疗现状与展望 [J]. 中国普外基础与临床杂志, 2004； 11(6)∶551.
21. 　Takeeda M, Yamato M, Kato S, et al. Cyclooxygenase iso-zymes involved in adaptive functional responses in rat stomach after barrier disruption [J]. J Pharmacol Exp Ther， 2003; 307(2)∶713.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Cyclooxygenase-2 on Hepatocellular Injury in Rats with Sepsis

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