IL-6、CAT、MPO在大鼠肝脏缺血再灌注损伤中的作用
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摘要
目的探讨白细胞介素-6(IL-6)、过氧化氢酶(CAT)、髓过氧化物酶(MPO)与大鼠肝脏缺血再灌注损伤(HIRI)关系及其损伤机制。方法选取6周龄SD大鼠150只,采用肝门部血流阻断法制备大鼠HIRI模型。采用简单随机分组原则将大鼠分为HIRI组(n=75)、缺血再灌注对照(Control)组(n=75);每组再分成3个亚组,分别为缺血再灌注后1 h组、3 h组、6 h组,每亚组各25只;分别在缺血再灌注后1、3、6 h抽取两组大鼠下腔静脉血液,检测血清中IL-6水平;切取适量肝组织,检测肝组织内的CAT、MPO活性,并用以评估两组各时间点HIRI情况。结果与Control组同期比较,HIRI组在肝脏缺血再灌注后1、3、6 h的IL-6含量、MPO活性高于Control组,但CAT活性较Control组降低(均P <0.05)。结论大鼠HIRI与急性炎性细胞因子IL-6及MPO释放增多以及与CAT释放抑制而导致氧自由基清除障碍有关。
Objective To investigate the relationship between interleukin-6(IL-6), catalase(CAT), myeloperoxidase(MPO)and hepatic ischemia-reperfusion injury(HIRI) in rats and its mechanism. Methods A total of 150 SD rats aged 6 weeks were selected and the HIRI model was established by blocking hepatic portal blood flow. Rats were divided into HIRI group(n = 75) and liver ischemia-reperfusion(Control) group(n = 75). Each group was divided into three subgroups: 1 h group, 3 h group and 6 h group after ischemia-reperfusion, with 25 rats in each subgroup. The inferior vena cava blood of the two groups were extracted at 1, 3 and 6 h after ischemia-reperfusion to detect the level of IL-6 in serum. The appropriate amount of liver tissue was cut, the activities of CAT and MPO in liver tissue were measured,and the situations of HIRI were evaluated at each time point in the two groups. Results Compared with the Control group, IL-6 and MPO activities in the HIRI group were higher than those in the Control group at 1, 3, and 6 h after hepatic ischemia-reperfusion, but the CAT activity was lower than that in the Control group(all P < 0.05). Conclusion The HIRI in rats is associated with the increase of IL-6 and MPO as well as with oxygen free radical scavenging disturbance caused by inhibition of CAT release.
Objective To investigate the relationship between interleukin-6(IL-6), catalase(CAT), myeloperoxidase(MPO)and hepatic ischemia-reperfusion injury(HIRI) in rats and its mechanism. Methods A total of 150 SD rats aged 6 weeks were selected and the HIRI model was established by blocking hepatic portal blood flow. Rats were divided into HIRI group(n = 75) and liver ischemia-reperfusion(Control) group(n = 75). Each group was divided into three subgroups: 1 h group, 3 h group and 6 h group after ischemia-reperfusion, with 25 rats in each subgroup. The inferior vena cava blood of the two groups were extracted at 1, 3 and 6 h after ischemia-reperfusion to detect the level of IL-6 in serum. The appropriate amount of liver tissue was cut, the activities of CAT and MPO in liver tissue were measured,and the situations of HIRI were evaluated at each time point in the two groups. Results Compared with the Control group, IL-6 and MPO activities in the HIRI group were higher than those in the Control group at 1, 3, and 6 h after hepatic ischemia-reperfusion, but the CAT activity was lower than that in the Control group(all P < 0.05). Conclusion The HIRI in rats is associated with the increase of IL-6 and MPO as well as with oxygen free radical scavenging disturbance caused by inhibition of CAT release.
引文
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[19]Jaeschke H,Woolbright BL.Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species[J].Transplant Rev,2012,26(2):103-114.
[20]Bhogal RH,Sutaria R,Afford SC.Hepatic liver ischemia/reperfusion injury:processes in inflammatory networks---a review[J].Liver Transpl,2010,16(9):1016-1032.
[2]李伟男,彭慈军,舒德军.肝脏缺血再灌注损伤的研究进展[J].世界华人消化杂志,2015,23(22):3554-3559.
[3]van Riel WG,van Golen RF,Reiniers MJ,et al.How much ischemia can the liver tolerate during resection?[J].Hepatobiliary Surg Nutr,2016,5(1):58.
[4]Guan LY,Fu PY,Li PD,et al.Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide[J].World J Gastrointest Surg,2014,6(7):122-128.
[5]Husted TL,Lentsch AB.The role of cytokines in pharmacological modulation of hepatic ischemia/reperfusion injury[J].Curr Pharm Des,2006,12(23):2867-2873.
[6]EliasmiróM,Jiménezcastro MB,Rodés J,et al.Current knowledge on oxidative stress in hepatic ischemia/reperfusion[J].Free Radic Res,2013,47(8):555-568.
[7]余淑珍,郭永清,郑李娜,等.SD大鼠急性全肝缺血再灌注模型建立与改良[J].中国药物与临床,2016,16(1):28-30.
[8]Liu A,Fang H,Dahmen U,et al.Chronic lithium treatment protects against liver ischemia/reperfusion injury in rats[J].Liver Transpl,2013,19(7):762-772.
[9]Pringle JH.V.Notes on the Arrest of Hepatic Hemorrhage Due to Trauma[J].Ann Surg,1908,48(4):541-549.
[9]Elias-MiróM,Jiménez-Castro MB,Rodés J,et al.Current knowledge on oxidative stress in hepatic ischemia/reperfusion[J].Free Radic Res,2013,47(8):555-568.
[10]彭方毅,李波.肝缺血再灌注损伤机制及相应保护措施的研究进展[J].现代医药卫生,2015(12):1821-1823.
[11]Zhou W,Zhang Y,Hosch MS,et al.Subcellular site of superoxide dismutase expression differentially controls AP-1activity and injury in mouse liver following ischemia/reperfusion[J].Hepatology,2001,33:902.
[12]王百林,苑伟,翟淑萍,等.利胆消黄汤对梗阻性黄疸兔肝细胞线粒体DNA损伤修复的研究[J].中华实验外科杂志,2015,32(11):2636-2638.
[13]王百林,苑伟,翟淑萍,等.梗阻性黄疸兔肝细胞线粒体氧化损伤的作用及机制[J].中华实验外科杂志,2014,31(11):2393-2395.
[14]Fergusonsmith AC,Chen YF,Newman MS,et al.Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21[J].Genomics,1988,2(3):203-208.
[15]Van d PT,Keogh CV,Guirao X,et al.Interleukin-6 genedeficient mice show impaired defense against pneumococcal pneumonia[J].J Infect Dis,1997,176(2):439-44.
[16]Faitot F,Besch C,Lebas B,et al.Interleukin 6 at reperfusion:a potent predictor of hepatic and extrahepatic early complications after liver transplantation[J].Clin Transplant,2018,25:e13357.
[17]Clavien PA.Sinusoidal endothelial cell injury during hepatic preservation and reperfusion[J].Hepatology,1998,28:281-285.
[18]Gao W,Bentley RC,Madden JF,et al.Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation[J].Hepatology,1998,27:1652-1660.
[19]Jaeschke H,Woolbright BL.Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species[J].Transplant Rev,2012,26(2):103-114.
[20]Bhogal RH,Sutaria R,Afford SC.Hepatic liver ischemia/reperfusion injury:processes in inflammatory networks---a review[J].Liver Transpl,2010,16(9):1016-1032.