Effects of Edaravone in Reversing Ischemia Reperfusion Injury of Liver_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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石臣磊 , 秦华东 , 丁超

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Keywords：

肝; 缺血再灌注损伤; 依达拉奉; 肿瘤坏死因子-α; 细胞凋亡

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目的研究依达拉奉影响肝脏缺血再灌注过程中TNF-α的表达情况，探讨依达拉奉对肝脏缺血再灌注损伤的逆转作用。方法将80只Wistar大鼠编号，根据计算机产生随机数字，前40为一组，后40为一组，分为实验组和对照组2组，建立常温下部分肝缺血再灌注损伤动物模型。在肝脏缺血再灌注损伤开始前1 h和开始时对实验组大鼠给予依达拉奉注射液10 ml，对照组则给予同等容量的生理盐水。分别于再灌注后0、1、2及4 h测定肝脏脂质过氧化物酶（LPO）和肝脏谷草转氨酶(AST) 浓度；应用RT-PCR法检测肝组织TNF-α mRNA含量，并测定肝组织和血清中TNF-α水平；应用TUNEL染色法检测缺血肝组织的细胞凋亡情况。结果再灌注后1、2及4 h，实验组大鼠肝脏LPO及AST浓度均明显低于对照组（P lt;0.001）；实验组再灌注后1 h时肝组织TNF-α mRNA表达量、肝组织和血清TNF-α含量均明显升高且达峰值，但均明显低于对照组（P lt;0.05）；再灌注后各时相实验组肝细胞凋亡率明显升高，但均明显低于对照组（P lt;0.05）。结论依达拉奉能抑制氧化应激反应，从而降低肝缺血再灌注损伤；并显著减少炎性细胞因子TNF-α的产生，抑制炎性反应的发生，减少肝细胞的凋亡。

Citation： 石臣磊,秦华东,丁超. Effects of Edaravone in Reversing Ischemia Reperfusion Injury of Liver. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(8): 887-889. doi: Copy

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2.	Hiranuma S, Ito K, Noda Y, et al. Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats [J]. J Gastroenterol Hepatol, 2007, 22(12): 21672172.
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5.	Totsuka O, Takeyoshi I, Tsutsumi H, et al. Effects of a free radical scavenger, MCI186, on ischemiareperfusion injury during extended liver resection in dogs [J]. Hepatogastroenterology, 2005, 52(65): 15451548.
6.	Taniguchi M, Uchinami M, Doi K, et al. Edaravone reduces ischemiareperfusion injury mediators in rat liver [J]. J Surg Res, 2007, 137(1): 6974.
7.	Perry BC, Soltys D, Toledo AH, et al. Tumor necrosis factorα in liver ischemia/reperfusion injury [J]. J Invest Surg, 2011, 24(4): 178188.
8.	Bhogal RH, Sutaria R, Afford SC. Hepatic liver ischemia/reperfusion injury: processes in inflammatory networks—A review [J]. Liver Transpl, 2011, 17(1): 95, author reply 96.
9.	Cheng MX, Chen ZZ, Cai YL, et al. Astragaloside Ⅳ protects against ischemia reperfusion in a murine model of orthotopic liver transplantation [J]. Transplant Proc, 2011, 43(5): 14561461.
10.	石臣磊，秦华东，石铁锋．依达拉奉对大鼠肝I/R损伤的保护作用 [J]．中国普通外科杂志， 2010， 19（1）： 2831．.
11.	HassanKhabbar S, Michel V, Charleshenry C, et al. Protective effect of postischemic treatment with transresveratrol on cytokine production and neutrophil recruitment by rat liver [J]. Biochimie, 2010, 92(4): 405410.
12.	Liu P, Xu B, Spokas E, et al. Role of endogenous nitric oxide in TNFalpha and IL1beta generation in hepatic ischemiarepefusion [J]. Shock, 2000, 13(3): 217223.
13.	石臣磊，秦华东． TNF和Eselectin的mRNA在依达拉奉抗大鼠肝缺血再灌注损伤中的表达 [J]．中华肝胆外科杂志， 2010， 16（4）： 312313．.
14.	Awad AS, El SA. Immunomodulatory effects of rosuvastatin on hepatic ischemia/reperfusion induced injury [J]. Immunopharmacol Immunotoxicol, 2010, 32(4): 555561.
15.	王科，王学浩，张峰，等．诱导HO1改善氧化应激状态减轻老年供肝缺血再灌注损伤 [J]．中国普外基础与临床杂志， 2005， 12（2）： 109112．.

1. Tapuria N, Junnarkar SP, Dutt N, et al. Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury [J]. HPB (Oxford), 2009, 11(2): 108117.
2. Hiranuma S, Ito K, Noda Y, et al. Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats [J]. J Gastroenterol Hepatol, 2007, 22(12): 21672172.
3. Zaouali MA, Ben AH, Padrissaaltés S, et al. Pharmacological strategies against cold ischemia reperfusion injury [J]. Expert Opin Pharmacother, 2010, 11(4): 537555.
4. 刘冰，秦华东，危国军，等．肝缺血再灌注损伤的基因治疗研究进展 [J]．中国普外基础与临床杂志， 2009， 16（4）： 336339．.
5. Totsuka O, Takeyoshi I, Tsutsumi H, et al. Effects of a free radical scavenger, MCI186, on ischemiareperfusion injury during extended liver resection in dogs [J]. Hepatogastroenterology, 2005, 52(65): 15451548.
6. Taniguchi M, Uchinami M, Doi K, et al. Edaravone reduces ischemiareperfusion injury mediators in rat liver [J]. J Surg Res, 2007, 137(1): 6974.
7. Perry BC, Soltys D, Toledo AH, et al. Tumor necrosis factorα in liver ischemia/reperfusion injury [J]. J Invest Surg, 2011, 24(4): 178188.
8. Bhogal RH, Sutaria R, Afford SC. Hepatic liver ischemia/reperfusion injury: processes in inflammatory networks—A review [J]. Liver Transpl, 2011, 17(1): 95, author reply 96.
9. Cheng MX, Chen ZZ, Cai YL, et al. Astragaloside Ⅳ protects against ischemia reperfusion in a murine model of orthotopic liver transplantation [J]. Transplant Proc, 2011, 43(5): 14561461.
10. 石臣磊，秦华东，石铁锋．依达拉奉对大鼠肝I/R损伤的保护作用 [J]．中国普通外科杂志， 2010， 19（1）： 2831．.
11. HassanKhabbar S, Michel V, Charleshenry C, et al. Protective effect of postischemic treatment with transresveratrol on cytokine production and neutrophil recruitment by rat liver [J]. Biochimie, 2010, 92(4): 405410.
12. Liu P, Xu B, Spokas E, et al. Role of endogenous nitric oxide in TNFalpha and IL1beta generation in hepatic ischemiarepefusion [J]. Shock, 2000, 13(3): 217223.
13. 石臣磊，秦华东． TNF和Eselectin的mRNA在依达拉奉抗大鼠肝缺血再灌注损伤中的表达 [J]．中华肝胆外科杂志， 2010， 16（4）： 312313．.
14. Awad AS, El SA. Immunomodulatory effects of rosuvastatin on hepatic ischemia/reperfusion induced injury [J]. Immunopharmacol Immunotoxicol, 2010, 32(4): 555561.
15. 王科，王学浩，张峰，等．诱导HO1改善氧化应激状态减轻老年供肝缺血再灌注损伤 [J]．中国普外基础与临床杂志， 2005， 12（2）： 109112．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Edaravone in Reversing Ischemia Reperfusion Injury of Liver

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