Protective Effect of Peroxisome Proliferator-Activated Receptor γ Activator 15-Deoxyprostaglandin J2 in Rat HepaticIschemia-Reperfusion Injury and Its Mechanism_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CAO X iaof ei , Z HA N G Feng , Z HA N G Wei , Z HA N G Yewei

L i ver T rans plantation Center , The Fi rst A f f i l iated Hos pi tal of N anj ing Medical Uni versi t y , N anj ing210029 , China;

Corresponding author：

Keywords：

Peroxisome proliferator2activated receptor γ ，15-deoxyprostaglandin J 2 ，Liver ischemia-reperfusion injury ，Nuclear factor-κB

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【 Abstract 】 Objective To investigate the protective effect of peroxisome proliferator-activated receptor γ (PPAR γ ) activator 15-deoxyprostaglandin J2 (15d-PGJ2) in rat hepatic ischemia-reperfusion injury and its mechanism. Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats, rats were randomly divided into 4 groups: sham operation group, ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2+GW9662 group. After reperfusion, serum AST and ALT levels were determined; the liver tissues were removed for measurement of activity of NF-κB and myeloperoxidase (MPO), TNF-α content and expression of ICAM-1. Results Compared with sham operation group, the serum levels of ALT and AST, and the activities of MPO and NF- κ B, TNF- α content and expression of ICAM-1 in ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2+GW9662 group were greatly improved (P ＜ 0.05). Compared with ischemia-reperfusion group, the serum levels of ALT and AST and the activities of MPO and NF- κ B, TNF- α content and expression of ICAM-1 in 15d-PGJ2 group were significantly decreased (P ＜ 0.05). Compared with 15d-PGJ2 group, the serum levels of ALT and AST, and the activities of MPO and NF- κ B, TNF- α content and the expression of ICAM-1 in 15d-PGJ2+GW9662 group were obviously increased (P ＜ 0.05). Conclusion PPAR γ activator 15d-PGJ2 could protect against ischemia-reperfusion injury in rats, with its possible mechanism of inhibiting NF-κB activation and down-regulating TNF-α content and ICAM-1 expression in a PPARγ dependent fashion.

Citation： CAO X iaof ei,Z HA N G Feng,Z HA N G Wei,Z HA N G Yewei. Protective Effect of Peroxisome Proliferator-Activated Receptor γ Activator 15-Deoxyprostaglandin J2 in Rat HepaticIschemia-Reperfusion Injury and Its Mechanism. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(4): 258-261. doi: Copy

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2. 　Escher P, Braissant O, Basu-Modak S, et al. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding [J]. Endocrinology，2001; 142(10)∶4195.
3. 　Powell WS. 15-Deoxy-delta12,14-PGJ2: endogenous PPARgamma ligand or minor eicosanoid degradation product? [J]. J Clin Invest，2003; 112(6)∶828.
4. 　Zingarelli B, Hake PW, Mangeshkar P, et al. Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-kappaB, heat shock factor 1, and Akt [J]. Shock，2007; 28(5)∶554.
5. 　Abdelrahman M, Collin M, Thiemermann C. The peroxisome proliferator-activated receptor-gamma ligand 15-deoxyDelta12,14 prostaglandin J2 reduces the organ injury in hemorrhagic shock [J]. Shock，2004; 22(6)∶555.
6. 　Collin M, Abdelrahman M, Thiemermann C. Endogenous ligands of PPAR-gamma reduce the liver injury in haemorrhagic shock [J]. Eur J Pharmacol，2004; 486(2)∶233.
7. 　Ohmori M, Miyashita F, Uchida H, et al. Effect of erythromycin on ischemia-reperfusion injury of liver in rats [J]. Transplant Proc，2000; 32(4)∶811.
8. 　Abdelrahman M, Sivarajah A, Thiemermann C. Beneficial eff-ects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock [J]. Cardiovasc Res，2005; 65(4)∶772.
9. 　Zingarelli B, Cook JA. Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation [J]. Shock，2005; 23(5)∶393.
10. 　刘江文, 程南生, 潘光栋, 等. PPARγ配体调控人胆囊上皮细胞炎性因子表达的实验研究 [J]. 中国普外基础与临床杂志, 2005; 12(4)∶336.
11. 　肖华, 张峰, 王学浩. PTEN基因在过氧化物酶体增殖物激活受体γ调节肝癌细胞生长中的作用 [J]. 中国普外基础与临床杂志, 2007; 14(4)∶413.
12. 　Lin TN, Cheung WM, Wu JS, et al. 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury [J]. Arterioscler Thromb Vasc Biol，2006; 26(3)∶481.
13. 　Takagi T, Naito Y, Ichikawa H, et al. A PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2), inhibited gastric mucosal injury induced by ischemia-reperfusion in rats [J]. Redox Rep，2004; 9(6)∶376.
14. 　Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function [J]. Nat Rev Mol Cell Biol，2007; 8(1)∶49.
15. 　Grivennikov SI, Kuprash DV, Liu ZG, et al. Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms [J]. Int Rev Cytol，2006; 252∶129.
16. 　Matsui N, Kasajima K, Hada M, et al. Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats [J]. J Toxicol Sci，2005; 30(2)∶103.
17. 　Luedde T, Trautwein C. Intracellular survival pathways in the liver [J]. Liver Int，2006; 26(10)∶1163.
18. 　Wang H, Li ZY, Wu HS, et al. Endogenous danger signals trigger hepatic ischemia/reperfusion injury through toll-like receptor 4/nuclear factor-kappaB pathway [J]. Chin Med J (Engl)，2007; 120(6)∶509.
19. 　Straus DS, Pascual G, Li M, et al. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappaB signaling pathway [J]. Proc Natl Acad Sci USA，2000; 97(9)∶4844.
20. 　 Scher JU, Pillinger MH. 15d-PGJ2: the anti-inflammatory pro-staglandin? [ J ] . Clin Immunol ， 2005; 114(2) ∶ 100.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Peroxisome Proliferator-Activated Receptor γ Activator 15-Deoxyprostaglandin J2 in Rat HepaticIschemia-Reperfusion Injury and Its Mechanism

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