Effect of p38MAPK Pathway on TNF-α mRNA and ICAM1 mRNA Expressions of Isolated Rabbit Liver Tissue During Early Stage of Cold Preservation and Reperfusion Period_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Yu , TANG Lijun , DAI Ruiwu , YAN Yong

The General Surgery Center of PLA, General Hospital of Chengdu Military Region, Chengdu 610083, China;

Corresponding author：

Keywords：

Liver; Ischemia-reperfusion; Injury; Mitogen activated protein kinase; Tumor necrosis factor; Intercellular adhesion molecule; Inhibitor

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Objective To study the effect of p38MAPK activity on tumor necrosis factor-α （TNF-α） mRNA and intercellular adhesion molecule 1 （ICAM1） mRNA expressions of isolated rabbit liver during early stage of cold preservation and reperfusion period. Methods Based on the cold preservation and reperfusion model of isolated rabbit liver, the animals were divided into inhibition group （n=12） with 3 μmol/L SB202190 (p38MAPK specificity inhibitor) in perfusate and control group （n=12） with no SB202190 in perfusate. Liver tissue samples were harvested at the time points of before resection, end of cold preservation, and different reperfusion period (10, 30, 60 and 120 min). Protein expression and activity of p38MAPK were detected by Western blot and immunoprecipitation respectively, expression of TNF-α mRNA was detected by RT-PCR, and expression of ICAM1 mRNA was detected by in situ hybridization. Results There was no obvious change of expression of p38MAPK protein in liver tissue both in two groups during the total period （P＞0.05）， and there was no statistically significant difference between two groups （P＞0.05）. At time points of end of cold preservation, 10, 30 and 60 min of reperfusion, the activity of p38MAPK in control group was significantly higher than that at the time points of before resection and 120 min of reperfusion (P＜0.01), and was also significantly higher than that in inhibition group at the same time points (P＜0.01). There was no significant difference in activity of p38MAPK among all time points in inhibition group (P＞0.05). The expressions of TNF-α mRNA and ICAM1 mRNA at the time points of before resection, end of cold preservation, and 10 and 30 min of reperfusion were significantly lower than those in 60 and 120 min of reperfusion in both two groups (P＜0.05, P＜0.01); The expressions of TNF-α mRNA and ICAM1 mRNA in inhibition group were significantly lower than those in control group at the time points of 60 and 120 min of reperfusion (P＜0.01). The activity of p38MAPK of liver tissue during cold preservation and reperfusion period was significantly correlated with the level of TNF-α mRNA and level of ICAM1 mRNA expression （r=0.996, P＜0.01； r=0.985, P＜0.01）. Conclusions These results suggest that p38MAPK pathway may regulate the expressions of TNF-α and ICAM1 at the level of transcription and the activation of p38MAPK can up-regulate TNF-α and ICAM1 expressions, which may be one of the important mechanisms to cause ischemia-reperfusion injury of isolated liver during cold preservation and reperfusion period.

Citation： WANG Yu,TANG Lijun,DAI Ruiwu,YAN Yong. Effect of p38MAPK Pathway on TNF-α mRNA and ICAM1 mRNA Expressions of Isolated Rabbit Liver Tissue During Early Stage of Cold Preservation and Reperfusion Period. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(6): 443-448. doi: Copy

1.	王雨，田伏洲，汤礼军, 等. p38信号转导途径对离体肝脏缺血再灌注损伤的影响 [J]. 中华肝脏病杂志, 2003; 11(3): 170-172.
2.	Jaeschke H, Farhood A. Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver [J]. Am J Physiol, 1991; 260(3 Pt 1): G355-G362.
3.	冉江华，郭永章，李立，等. 重组人生长激素对大鼠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， 2006； 13（5）： 555-559.
4.	Jamieson NV, Lindell S, Sundberg R, et al. An analysis of the components in UW solution using the isolated perfused rabbit liver [J]. Transplantation, 1988; 46(4): 512-516.
5.	简文，樊爱琳，尹文，等. 山莨菪碱治疗兔创伤性急性肺损伤分子生物学机制的实验研究 [J]. 第四军医大学学报，2008； 29(11)： 985-987.
6.	汤礼军, 田伏洲, 王雨, 等. 缺血-再灌注肝脏组织中ICAM-1基因的表达 [J]. 中国病理生理杂志, 2001； 17(12): 1246-1248.
7.	Chen XL, Xia ZF, Ben DF, et al. Role of p38 mitogen-activated protein kinase in lung injury after burn trauma [J]. Shock, 2003; 19(5): 475-479.
8.	Dawson DA, Martin D, Hallenbeck JM. Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat [J]. Neurosci Lett, 1996; 218(1): 41-44.
9.	Dinarello CA, Ikejima T, Warner SJ, et al. Interleukin 1 induces interleukin 1. Ⅰ. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro [J]. J Immunol, 1987; 139(6): 1902-1910.
10.	崔尧元，余勇，张晓彪, 等. 细胞间粘附分子1、肿瘤坏死因子α转录水平在缺血再灌注大鼠脑皮质中表达的相关性 [J]. 中华实验外科杂志， 1999; 16(5): 442-443.
11.	孙圣刚, 李小凤, 童萼塘，等. 大鼠脑缺血再灌注后脑组织TNF与ICAM表达的实验研究 [J]. 同济医科大学学报， 1999; 28(6): 489-491.
12.	Bhargava A, Bradley NJ, Burroughs AK, et al. Expression of intercellular adhesion molecule-1 and CD4/CD8 lymphocyte markers in perioperative liver allograft biopsies [J]. Transplant Proc, 1995; 27(5): 2814-2815.
13.	Arbabi S, Garcia I, Bauer GJ, et al. Alcohol (ethanol) inhibits IL-8 and TNF: role of the p38 pathway [J]. J Immunol, 1999; 162(12): 7441-7445.
14.	Hafez T, Moussa M, Nesim I, et al. The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury [J]. J Surg Res, 2007; 138(1): 88-99.
15.	徐锋,　苏琪,　戴朝六,　等. 前列腺素E1对梗阻性黄疸肝缺血再灌注时肝组织细胞间黏附分子-1表达的影响　[J].　广东医学,　2009;　30(1): 37-38.
16.	袁晓园, 陈隆典. 肝免疫耐受发生的相关因素和机制研究 [J]. 国际免疫学杂志, 2006; 29(1): 26-30.
17.	张维山, 冷启新, 王金平，等. 转录因子NF-κB在内毒素休克中的作用 [J]. 解剖科学进展,　2005; 11(2): 161-163.
18.	刘佃香. 慢性乙型肝炎及乙肝肝硬化患者的血小板功能相关性分析 [J]. 医学理论与实践, 2008; 21(8): 959-960.
19.	黄翠萍, 杨和平, 张珍祥, 等. p38蛋白激酶对支气管哮喘大鼠Th2类细胞因子表达的调控 [J]. 中国病理生理杂志, 2006; 22(2): 311-313.
20.	Tudhope SJ, Finney-Hayward TK, Nicholson AG, et al. Different mitogen-activated protein kinase-dependent cytokine responses in cells of the monocyte lineage [J]. J Pharmacol Exp Ther, 2008; 324(1): 306-312.
21.	姜勇，刘爱华，张琳，等. 脂多糖激活p38在诱导肿瘤坏死因子α基因表达中的作用 [J]. 中华医学杂志， 1999； 79（5）： 360-364.
22.	刘少华，马可，许兵，等. 一氧化碳对脂多糖诱导大鼠肠道损伤的影响 [J]. 中国普外基础与临床杂志, 2008; 15(3): 174-179.
23.	Yan W, Zhao K, Jiang Y, et al. Role of p38 MAPK in ICAM-1 expression of vascular endothelial cells induced by lipopolysaccharide 　[J]. Shock, 2002; 17(5): 433-438.
24.	Tamura DY, Moore EE, Johnson JL, et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells [J]. Surgery, 1998; 124(2): 403-407.
25.	Kacimi R, Karliner JS, Koudssi F, et al. Expression and regulation of adhesion molecules in cardiac cells by cytokines: response to acute hypoxia [J]. Circ Res, 1998; 82(5): 576-586.
26.	Saha RN, Jana M, Pahan K. MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65 [J]. J Immunol, 2007; 179(10): 7101-7109.
27.	Olson CM, Hedrick MN, Izadi H,　 et al. p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens [J]. Infect Immun, 2007; 75(1): 270-277.
28.	陈旭林, 夏照帆, 贾一韬，等. p38丝裂原活化蛋白激酶对严重烧伤大鼠肝脏激活蛋白-1和核因子-κB的影响 [J/CD]. 中华损伤与修复杂志(电子版), 2008; 3(2): 150-155.
29.	马跃峰, 李相成, 姚爱华，等. 缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义 [J]. 中国普外基础与临床杂志, 2006; 13(5): 531-534.

1. 王雨，田伏洲，汤礼军, 等. p38信号转导途径对离体肝脏缺血再灌注损伤的影响 [J]. 中华肝脏病杂志, 2003; 11(3): 170-172.
2. Jaeschke H, Farhood A. Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver [J]. Am J Physiol, 1991; 260(3 Pt 1): G355-G362.
3. 冉江华，郭永章，李立，等. 重组人生长激素对大鼠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， 2006； 13（5）： 555-559.
4. Jamieson NV, Lindell S, Sundberg R, et al. An analysis of the components in UW solution using the isolated perfused rabbit liver [J]. Transplantation, 1988; 46(4): 512-516.
5. 简文，樊爱琳，尹文，等. 山莨菪碱治疗兔创伤性急性肺损伤分子生物学机制的实验研究 [J]. 第四军医大学学报，2008； 29(11)： 985-987.
6. 汤礼军, 田伏洲, 王雨, 等. 缺血-再灌注肝脏组织中ICAM-1基因的表达 [J]. 中国病理生理杂志, 2001； 17(12): 1246-1248.
7. Chen XL, Xia ZF, Ben DF, et al. Role of p38 mitogen-activated protein kinase in lung injury after burn trauma [J]. Shock, 2003; 19(5): 475-479.
8. Dawson DA, Martin D, Hallenbeck JM. Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat [J]. Neurosci Lett, 1996; 218(1): 41-44.
9. Dinarello CA, Ikejima T, Warner SJ, et al. Interleukin 1 induces interleukin 1. Ⅰ. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro [J]. J Immunol, 1987; 139(6): 1902-1910.
10. 崔尧元，余勇，张晓彪, 等. 细胞间粘附分子1、肿瘤坏死因子α转录水平在缺血再灌注大鼠脑皮质中表达的相关性 [J]. 中华实验外科杂志， 1999; 16(5): 442-443.
11. 孙圣刚, 李小凤, 童萼塘，等. 大鼠脑缺血再灌注后脑组织TNF与ICAM表达的实验研究 [J]. 同济医科大学学报， 1999; 28(6): 489-491.
12. Bhargava A, Bradley NJ, Burroughs AK, et al. Expression of intercellular adhesion molecule-1 and CD4/CD8 lymphocyte markers in perioperative liver allograft biopsies [J]. Transplant Proc, 1995; 27(5): 2814-2815.
13. Arbabi S, Garcia I, Bauer GJ, et al. Alcohol (ethanol) inhibits IL-8 and TNF: role of the p38 pathway [J]. J Immunol, 1999; 162(12): 7441-7445.
14. Hafez T, Moussa M, Nesim I, et al. The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury [J]. J Surg Res, 2007; 138(1): 88-99.
15. 徐锋,　苏琪,　戴朝六,　等. 前列腺素E1对梗阻性黄疸肝缺血再灌注时肝组织细胞间黏附分子-1表达的影响　[J].　广东医学,　2009;　30(1): 37-38.
16. 袁晓园, 陈隆典. 肝免疫耐受发生的相关因素和机制研究 [J]. 国际免疫学杂志, 2006; 29(1): 26-30.
17. 张维山, 冷启新, 王金平，等. 转录因子NF-κB在内毒素休克中的作用 [J]. 解剖科学进展,　2005; 11(2): 161-163.
18. 刘佃香. 慢性乙型肝炎及乙肝肝硬化患者的血小板功能相关性分析 [J]. 医学理论与实践, 2008; 21(8): 959-960.
19. 黄翠萍, 杨和平, 张珍祥, 等. p38蛋白激酶对支气管哮喘大鼠Th2类细胞因子表达的调控 [J]. 中国病理生理杂志, 2006; 22(2): 311-313.
20. Tudhope SJ, Finney-Hayward TK, Nicholson AG, et al. Different mitogen-activated protein kinase-dependent cytokine responses in cells of the monocyte lineage [J]. J Pharmacol Exp Ther, 2008; 324(1): 306-312.
21. 姜勇，刘爱华，张琳，等. 脂多糖激活p38在诱导肿瘤坏死因子α基因表达中的作用 [J]. 中华医学杂志， 1999； 79（5）： 360-364.
22. 刘少华，马可，许兵，等. 一氧化碳对脂多糖诱导大鼠肠道损伤的影响 [J]. 中国普外基础与临床杂志, 2008; 15(3): 174-179.
23. Yan W, Zhao K, Jiang Y, et al. Role of p38 MAPK in ICAM-1 expression of vascular endothelial cells induced by lipopolysaccharide 　[J]. Shock, 2002; 17(5): 433-438.
24. Tamura DY, Moore EE, Johnson JL, et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells [J]. Surgery, 1998; 124(2): 403-407.
25. Kacimi R, Karliner JS, Koudssi F, et al. Expression and regulation of adhesion molecules in cardiac cells by cytokines: response to acute hypoxia [J]. Circ Res, 1998; 82(5): 576-586.
26. Saha RN, Jana M, Pahan K. MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65 [J]. J Immunol, 2007; 179(10): 7101-7109.
27. Olson CM, Hedrick MN, Izadi H,　 et al. p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens [J]. Infect Immun, 2007; 75(1): 270-277.
28. 陈旭林, 夏照帆, 贾一韬，等. p38丝裂原活化蛋白激酶对严重烧伤大鼠肝脏激活蛋白-1和核因子-κB的影响 [J/CD]. 中华损伤与修复杂志(电子版), 2008; 3(2): 150-155.
29. 马跃峰, 李相成, 姚爱华，等. 缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义 [J]. 中国普外基础与临床杂志, 2006; 13(5): 531-534.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of p38MAPK Pathway on TNF-α mRNA and ICAM1 mRNA Expressions of Isolated Rabbit Liver Tissue During Early Stage of Cold Preservation and Reperfusion Period

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