Immunity mechanism of ischemia postconditioning in preventing from hepatic ischemia-reperfusion injury in liver cirrhotic rats

doi:10.3877/cma.j.issn.2095-3232.2014.06.010

Abstract

Abstract:

Objective

To investigate the protective effects and its mechanism of ischemia postconditioning (IPO) in hepatic ischemia-reperfusion injury (IRI) in liver cirrhotic rats.

Methods

Thirty liver cirrhotic Sprague-Dawley (SD) rats were randomly divided into three groups according to the random table methods: ischemia postconditioning (IPO) group, IRI group, and pure hepatectomy (PH) group with 10 rats in each group. Rats in IPO group underwent partial hepatectomy (40%), and the first portal was occluded for 20 min, then 3 times of ischemia-reperfusion were performed, and finally continuous reperfusion. Rats in IRI group underwent partial hepatectomy (40%), and the first portal was occluded for 20 min, then continuous reperfusion was performed. Rats in PH group underwent partial hepatectomy (40%) only. Inferior vena cava blood was collected at 6, 24 h after operation. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), proportion of cluster of differentiation (CD) 4⁺, CD8⁺, regulatory T cells (Treg) and levels of interleukin (IL)-4, IL-10 were tested. Comparison of three groups was conducted by one way analysis of variance and pairwise comparison by LSD-t test.

Results

After 6 h reperfusion, levels of ALT and AST in IPO group [(1 623±378) , (1 993±469) U/L] were significantly lower than those in IRI group [(2 690±549) , (3 020±577) U/L] (LSD-t=-4.21, -3.72; P<0.05). After 24 h reperfusion, levels of ALT and AST in IPO group [(307±76) , (555±137) U/L] were still significantly lower than those in IRI group [(518±105) , (1 050±355) U/L] (LSD-t=-4.06, -3.37; P<0.05). After 6 h reperfusion, proportion of CD4⁺, CD8⁺, CD4⁺/CD8⁺ ratio, Treg, and levels of IL-4, IL-10 in IPO group were (57±5) %, (25±3) %, 2.3±0.5, (8.9±0.4) %, (1.27±0.25) mg/L, (0.61±0.03) mg/L, respectively. While in IRI group, they were (52±6)%, (12±3) %, 4.5±0.8, (7.3±0.3) %, (0.66±0.11) mg/L, (0.34±0.06) mg/L, respectively. In IPO group, CD8⁺, Treg, IL-4 and IL-10 increased significantly, while CD4⁺/CD8⁺ ratio decreased significantly, compared with those in IRI group (LSD-t= 7.74, 6.67, 5.52, 9.31, -6.69; P<0.05).

Conclusion

IPO can prevent from hepatic IRI injury in liver cirrhotic rats through decreasing the immune injury.

Key words: Reperfusion injury, Rats, Liver cirrhosis, experimental, Ischemic postconditioning, T-lymphocyte subsets, Interleukin-4, Interleukin-10

Fei Ji, Yunpeng Hua, Peien Jian, Shunjun Fu, Kun Zhao, Jiaming Lai, Shaoqiang Li. Immunity mechanism of ischemia postconditioning in preventing from hepatic ischemia-reperfusion injury in liver cirrhotic rats[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2014, 03(06): 371-374.

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References 20

[1]	Theodoraki K, Arkadopoulos N, Nastos C, et al. Small liver remnants are more vulnerable to ischemia/reperfusion injury after extended hepatectomies: a case-control study[J]. World J Surg, 2012, 36(12):2895-2900.
[2]	Akhtar MZ, Henderson T, Sutherland A, et al. Novel approaches to preventing ischemia-reperfusion injury during liver transplantation[J]. Transplant Proc, 2013, 45(6):2083-2092.
[3]	Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, et al. Factors in the pathophysiology of the liver ischemia-reperfusion injury[J]. J Surg Res, 2008, 147(1):153-159.
[4]	Linfert D, Chowdhry T, Rabb H. Lymphocytes and ischemia-reperfusion injury[J]. Transplant Rev, 2009, 23(1):1-10.
[5]	Yang X, Bai H, Wang Y, et al. Deletion of regulatory T cells supports the development of intestinal ischemia-reperfusion injuries[J]. J Surg Res, 2013, 184(2):832-837.
[6]	Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol Heart Circ Physiol, 2003, 285(2):H579-588.
[7]	van den Akker EK, Manintveld OC, Hesselink DA, et al. Protection against renal ischemia-reperfusion injury by ischemic postconditioning[J]. Transplantation, 2013, 95(11):1299-1305.
[8]	Lintz JA, Dalio MB, Joviliano EE, et al. Ischemic pre and postconditioning in skeletal muscle injury produced by ischemia and reperfusion in rats[J]. Acta Cir Bras, 2013, 28(6):441-446.
[9]	Liu J, Xu Q, Wang H, et al. Neuroprotection of ischemic postconditioning by downregulating the postsynaptic signaling mediated by kainate receptors[J]. Stroke, 2013, 44(7):2031-2035.
[10]	Lin HC, Lee TK, Tsai CC, et al. Ischemic postconditioning protects liver from ischemia-reperfusion injury by modulating mitochondrial permeability transition[J]. Transplantation, 2012, 93(3):265-271.
[11]	华赟鹏，李绍强，赖佳明，等．体重监测下渐进性口服二乙基亚硝胺诱导肝硬变大鼠模型的研究[J]．中国普外基础与临床杂志,2009,16(8):625-627.
[12]	梁力建，华赟鹏，黄洁夫．肝缺血再灌注对肝硬化大鼠的损伤作用[J]．中华肝胆外科杂志, 2002, 8(5):283-286.
[13]	Uchida Y, Ke B, Freitas MC, et al. The emerging role of T cell immunoglobulin mucin-1 in the mechanism of liver ischemia and reperfusion injury in the mouse[J]. Hepatology, 2010, 51(4):1363-1372.
[14]	Sharma AK, Laubach VE, Ramos SI, et al. Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg, 2010, 139(2):474-482.
[15]	李敏如，汪根树，汪国营，等．慢性重型肝炎和肝细胞肝癌患者肝移植围手术期T淋巴细胞亚群及其功能的变化[J/CD]．中华肝脏外科手术学电子杂志，2013, 2(3):153-158.
[16]	Saito K, Wagatsuma T, Toyama H, et al. Sepsis is characterized by the increases in percentages of circulating CD4⁺CD25⁺ regulatory T cells and plasma levels of soluble CD25[J]. Tohoku J Exp Med, 2008, 216(1):61-68.
[17]	Venet F, Chung CS, Kherouf H, et al. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients[J]. Intensive Care Med, 2009, 35(4):678-686.
[18]	Kinsey GR, Sharma R, Huang L, et al. Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury[J]. J Am Soc Nephrol, 2009, 20(8):1744-1753.
[19]	Kim MG, Koo TY, Yan JJ, et al. IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells[J]. J Am Soc Nephrol, 2013, 24(10):1529-1536.
[20]	Arias-Diaz J, Ildefonso JA, Munoz JJ, et al. Both tacrolimus and sirolimus decrease Th1/Th2 ratio, and increase regulatory T lymphocytes in the liver after ischemia/reperfusion[J]. Lab Invest, 2009, 89(4):433-445.

组别	鼠数	CD4⁺（%）		CD8⁺（%）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	57±5	39±5	25±3	18±3
IRI组	10	52±6	33±4	12±3	17±2
肝切组	10	40±6	36±5	19±2	18±2
组别	鼠数	CD4⁺/CD8⁺比值		Treg（%）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	2.3±0.5	2.2±0.4	8.9±0.4	7.4±0.5
IRI组	10	4.5±0.8	2.0±0.3	7.3±0.3	9.5±0.7
肝切组	10	2.2±0.2	2.1±0.4	7.1±0.4	7.5±0.5
组别	鼠数	IL-4（mg/L）		IL-10（mg/L）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	1.27±0.25	0.70±0.17	0.61±0.03	0.29±0.07
IRI组	10	0.66±0.11	0.69±0.21	0.34±0.06	0.55±0.08
肝切组	10	0.73±0.14	0.71±0.10	0.31±0.05	0.23±0.06

组别	鼠数	CD4⁺（%）		CD8⁺（%）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	57±5	39±5	25±3	18±3
IRI组	10	52±6	33±4	12±3	17±2
肝切组	10	40±6	36±5	19±2	18±2
组别	鼠数	CD4⁺/CD8⁺比值		Treg（%）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	2.3±0.5	2.2±0.4	8.9±0.4	7.4±0.5
IRI组	10	4.5±0.8	2.0±0.3	7.3±0.3	9.5±0.7
肝切组	10	2.2±0.2	2.1±0.4	7.1±0.4	7.5±0.5
组别	鼠数	IL-4（mg/L）		IL-10（mg/L）
组别	鼠数	6 h	24 h	6 h	24 h
IPO组	10	1.27±0.25	0.70±0.17	0.61±0.03	0.29±0.07
IRI组	10	0.66±0.11	0.69±0.21	0.34±0.06	0.55±0.08
肝切组	10	0.73±0.14	0.71±0.10	0.31±0.05	0.23±0.06

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