Effect of Cyclooxygenase-2 on Prostaglandin I2 Receptor/Thromboxane A2 Receptor in Ischemia Reperfusion Injury after Liver Transplantation in Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Liping ¹ , LI Yuming ² , SHI Bin ¹ , LI Xun ² , ZHOU Wence ² , LI Bin ¹ , ZHANG Hui ² , LIU Tao ² , HE Wenting ²

1.Department of ICU, The First Hospital of Lanzhou University, Lanzhou 730000, China;;
2.Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

Keywords：

Liver transplantation; Ischemia reperfusion injury; Cyclooxygenase-2; Prostaglandin I2 receptor; Thromboxane A2 receptor

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Objective To study the interaction and mechanism of prostaglandin I2 (PGI2) receptor/thromboxane A2 (TxA2) receptor (IP/TP) and cyclooxygenase-2 (COX-2) in ischemia reperfusion injury after liver transplantation of rat.
Methods Rats were randomly divided into three groups: control group （n=16), orthotropic liver transplantation group （n=32) and nimesulide intervention group （n=32). The samples were obtained at 3 h, 6 h, 12 h and 24 h after operation. The expressions of COX-2, IP and TP mRNA were detected by RT-PCR. Immunohistochemistry was used to detect the localization and expression of COX-2. Hematoxylin Eosin staining was used to classify the injury extent of liver. Serum ALT and AST levels were detected to evaluate the changes of liver enzyme.
Results COX-2 protein expression detected by immunohistochemistry in orthotropic liver transplantation group mainly distributed in the district of liver sinusoidal endothelial cells, liver cells and macrophage cells, which was significantly higher than control group and nimesulide intervention group. Expressions of IP mRNA, TP mRNA and COX-2 mRNA in the orthotropic liver transplantation group were significantly increased than those in control group (P＜0.05), and the ratio of IP/TP increased (P＜0.05). Expressions of IP mRNA and TP mRNA in nimesulide intervention group were significantly lower than that in the orthotropic liver transplantation group at 6 h and 12 h after operation (P＜0.05), and the ratio of IP/TP decreased at 3 h, 6 h and 24 h after operation (P＜0.05). The expression of COX-2 mRNA in nimesulide intervention group was significantly lower than that in the orthotropic liver transplantation group at 6 h, 12 h and 24 h after operation. In orthotropic liver transplantation group liver injury was obvious by HE staining, and more severve than that in nimesulide intervention group. Serum AST (each time) and ALT (3 h, 6 h and 12 h) levels in the orthotropic liver transplantation group were significantly higher than that in control group and nimesulide intervention group (P＜0.05) and peaked at 6 h after operation.
Conclusion The balance of IP/TP takes part in and plays an important role in the ischemia reperfusion injury of liver transplantation. Changing imbalance of IP/TP may reduce liver transplantation ischemia reperfusion injury by inhibiting COX-2 expression.

Citation： LIU Liping,LI Yuming,SHI Bin,LI Xun,ZHOU Wence,LI Bin,ZHANG Hui,LIU Tao,HE Wenting. Effect of Cyclooxygenase-2 on Prostaglandin I2 Receptor/Thromboxane A2 Receptor in Ischemia Reperfusion Injury after Liver Transplantation in Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(7): 534-539. doi: Copy

1.	Fondevila C, Busuttil RW, KupiecWeglinski JW. Hepatic ischemia/reperfusion injury-a fresh look [Ｊ]. Exp Mol Pathol, 2003; 74(2): 8693.
2.	Guo Y, Bao W, Wu WJ, et al. Evidence for an essential role of cyclooxygenase2 as a mediator of the late phase of ischemic preconditioning in mice [Ｊ]. Basic Res Cardiol, 2000； 95(6): 479484.
3.	李斌，李玉民，李汛，等. 环氧合酶2对脓毒症大鼠肝损伤的影响 [Ｊ]. 中国普外基础与临床杂志， 2008； 15（4）： 266270.
4.	涂兵，严律南，刘智敏. 缺血预处理对大鼠移植肝脏缺血再灌注损伤的保护作用 [Ｊ]. 中国普外基础与临床杂志， 2002； 9（2）： 8992.
5.	曹晓飞，张峰，张伟，等. PPARγ激动剂15dPGJ2在大鼠肝脏缺血再灌注损伤中的保护作用及机理 [Ｊ]. 中国普外基础与临床杂志， 2008； 15（4）： 258261.
6.	李涛，唐华美，孙星，等. “二袖套法”大鼠原位肝移植的技术改进 [Ｊ]. 中国普通外科杂志, 2005； 14（7）: 486488.
7.	Kopff M, Kopff A, Kowalczyk E. [The effect of nonsteroidal antiinflammatory drugs on oxidative/antioxidative balance] [Ｊ]. Pol Merkur Lekarski, 2007; 23(135): 184187.
8.	Nanji AA, Miao L, Thomas P, et al. Enhanced cyclooxygenase2 gene expression in alcoholic liver disease in the rat [Ｊ]. Gastroenterology, 1997; 112(3): 943951.
9.	Ganey PE, Barton YW, Kinser S, et al. Involvement of cyclooxygenase2 in the potentiation of allyl alcoholinduced liver injury by bacterial lipopolysaccharide [Ｊ]. Toxicol Appl Pharmacol, 2001; 174(2): 113121.
10.	Mathurin P, Deng QG, Keshavarzian A, et al. Exacerbation of alcoholic liver injury by enteral endotoxin in rats [Ｊ]. Hepatology, 2000; 32(5): 10081017.
11.	Hamada T, Tsuchihashi S, Avanesyan A, et al. Cyclooxygenase2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury [Ｊ]. J Immunol, 2008; 180(3): 18431853.
12.	Ozturk H, Gezici A, Ozturk H. The effect of celecoxib, a selective COX2 inhibitor, on liver ischemia/reperfusioninduced oxidative stress in rats [Ｊ]. Hepatol Res, 2006; 34(2): 7683.
13.	Bolli R, Shinmura K, Tang XL, et al. Discovery of a new function of cyclooxygenase (COX)2: COX2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning [Ｊ]. Cardiovasc Res, 2002; 55(3): 506519.
14.	Tsukada K, Hasegawa T, Tsutsumi S, et al. Roles of cyclooxygenase2 in tissue injury during hemorrhagic shock [Ｊ]. Shock, 2000; 13(5): 392396.
15.	Hei ZQ, Huang HQ, Luo CF, et al. Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation [Ｊ]. World J Gastroenterol， 2006; 12(25): 40494051.
16.	Wilson SJ, Smyth EM. Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylationdependent interaction with the subunit of cGMP phosphodiesterase 6 [Ｊ]. J Biol Chem, 2006; 281(17): 1178011786.
17.	Mochizuki M, Ishii Y, Itoh K, et al. Role of 15deoxy △12,14 prostaglandin J2 and Nrf2 pathways in protection against acute lung injury [Ｊ]. Am J Respir Crit Care Med, 2005; 171(11): 12601266.
18.	Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2 [Ｊ]. Science, 2002; 296(5567): 539541.
19.	Hirata T, Kakizuka A, Ushikubi F, et al. Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder [Ｊ]. J Clin Invest, 1994; 94(4): 16621667.
20.	Kobayashi T, Tahara Y, Matsumoto M, et al. Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoEdeficient mice [Ｊ]. J Clin Invest, 2004; 114(6): 784794.
21.	Egan KM, Wang M, Fries S, et al. Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase2 inhibition combined with thromboxane receptor antagonism [Ｊ]. Circulation, 2005; 111(3): 334342.
22.	Bachschmid M, Thurau S, Zou MH, et al. Endothelial cell activation by endotoxin involves superoxide/NOmediated nitration of prostacyclin synthase and thromboxane receptor stimulation [Ｊ]. FASEB J, 2003; 17(8): 914916.
23.	Zou MH, Bachschmid M. Hypoxiareoxygenation triggers coronary vasospasm in isolated bovine coronary arteries via tyrosine nitration of prostacyclin synthase [Ｊ]. J Exp Med, 1999； 190(1): 135139.
24.	Gendron ME, Thorin E. A change in the redox environment and thromboxane A2 production precede endothelial dysfunction in mice [Ｊ]. Am J Physiol Heart Circ Physiol, 2007; 293(4): H2508H2515.

1. Fondevila C, Busuttil RW, KupiecWeglinski JW. Hepatic ischemia/reperfusion injury-a fresh look [Ｊ]. Exp Mol Pathol, 2003; 74(2): 8693.
2. Guo Y, Bao W, Wu WJ, et al. Evidence for an essential role of cyclooxygenase2 as a mediator of the late phase of ischemic preconditioning in mice [Ｊ]. Basic Res Cardiol, 2000； 95(6): 479484.
3. 李斌，李玉民，李汛，等. 环氧合酶2对脓毒症大鼠肝损伤的影响 [Ｊ]. 中国普外基础与临床杂志， 2008； 15（4）： 266270.
4. 涂兵，严律南，刘智敏. 缺血预处理对大鼠移植肝脏缺血再灌注损伤的保护作用 [Ｊ]. 中国普外基础与临床杂志， 2002； 9（2）： 8992.
5. 曹晓飞，张峰，张伟，等. PPARγ激动剂15dPGJ2在大鼠肝脏缺血再灌注损伤中的保护作用及机理 [Ｊ]. 中国普外基础与临床杂志， 2008； 15（4）： 258261.
6. 李涛，唐华美，孙星，等. “二袖套法”大鼠原位肝移植的技术改进 [Ｊ]. 中国普通外科杂志, 2005； 14（7）: 486488.
7. Kopff M, Kopff A, Kowalczyk E. [The effect of nonsteroidal antiinflammatory drugs on oxidative/antioxidative balance] [Ｊ]. Pol Merkur Lekarski, 2007; 23(135): 184187.
8. Nanji AA, Miao L, Thomas P, et al. Enhanced cyclooxygenase2 gene expression in alcoholic liver disease in the rat [Ｊ]. Gastroenterology, 1997; 112(3): 943951.
9. Ganey PE, Barton YW, Kinser S, et al. Involvement of cyclooxygenase2 in the potentiation of allyl alcoholinduced liver injury by bacterial lipopolysaccharide [Ｊ]. Toxicol Appl Pharmacol, 2001; 174(2): 113121.
10. Mathurin P, Deng QG, Keshavarzian A, et al. Exacerbation of alcoholic liver injury by enteral endotoxin in rats [Ｊ]. Hepatology, 2000; 32(5): 10081017.
11. Hamada T, Tsuchihashi S, Avanesyan A, et al. Cyclooxygenase2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury [Ｊ]. J Immunol, 2008; 180(3): 18431853.
12. Ozturk H, Gezici A, Ozturk H. The effect of celecoxib, a selective COX2 inhibitor, on liver ischemia/reperfusioninduced oxidative stress in rats [Ｊ]. Hepatol Res, 2006; 34(2): 7683.
13. Bolli R, Shinmura K, Tang XL, et al. Discovery of a new function of cyclooxygenase (COX)2: COX2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning [Ｊ]. Cardiovasc Res, 2002; 55(3): 506519.
14. Tsukada K, Hasegawa T, Tsutsumi S, et al. Roles of cyclooxygenase2 in tissue injury during hemorrhagic shock [Ｊ]. Shock, 2000; 13(5): 392396.
15. Hei ZQ, Huang HQ, Luo CF, et al. Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation [Ｊ]. World J Gastroenterol， 2006; 12(25): 40494051.
16. Wilson SJ, Smyth EM. Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylationdependent interaction with the subunit of cGMP phosphodiesterase 6 [Ｊ]. J Biol Chem, 2006; 281(17): 1178011786.
17. Mochizuki M, Ishii Y, Itoh K, et al. Role of 15deoxy △12,14 prostaglandin J2 and Nrf2 pathways in protection against acute lung injury [Ｊ]. Am J Respir Crit Care Med, 2005; 171(11): 12601266.
18. Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2 [Ｊ]. Science, 2002; 296(5567): 539541.
19. Hirata T, Kakizuka A, Ushikubi F, et al. Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder [Ｊ]. J Clin Invest, 1994; 94(4): 16621667.
20. Kobayashi T, Tahara Y, Matsumoto M, et al. Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoEdeficient mice [Ｊ]. J Clin Invest, 2004; 114(6): 784794.
21. Egan KM, Wang M, Fries S, et al. Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase2 inhibition combined with thromboxane receptor antagonism [Ｊ]. Circulation, 2005; 111(3): 334342.
22. Bachschmid M, Thurau S, Zou MH, et al. Endothelial cell activation by endotoxin involves superoxide/NOmediated nitration of prostacyclin synthase and thromboxane receptor stimulation [Ｊ]. FASEB J, 2003; 17(8): 914916.
23. Zou MH, Bachschmid M. Hypoxiareoxygenation triggers coronary vasospasm in isolated bovine coronary arteries via tyrosine nitration of prostacyclin synthase [Ｊ]. J Exp Med, 1999； 190(1): 135139.
24. Gendron ME, Thorin E. A change in the redox environment and thromboxane A2 production precede endothelial dysfunction in mice [Ｊ]. Am J Physiol Heart Circ Physiol, 2007; 293(4): H2508H2515.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Cyclooxygenase-2 on Prostaglandin I2 Receptor/Thromboxane A2 Receptor in Ischemia Reperfusion Injury after Liver Transplantation in Rats

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