不同品系大鼠之间肝移植排斥反应的比较研究

叶志坚; 杨中萌; 王效民

doi:10.3969/j.issn.1674-7445.2014.05.006

不同品系大鼠之间肝移植排斥反应的比较研究

doi: 10.3969/j.issn.1674-7445.2014.05.006

1.
361004 厦门大学附属中山医院胃肠外科(叶志坚)
2.
中山大学附属第五医院骨科(杨中萌)
3.
361004 厦门大学附属中山医院肝胆外科(王效民)

基金项目:

国家自然科学基金 81171976

卫生和计划生育委员会科学研究基金-福建省卫生教育联合攻关计划 WKJ2005-2-020

详细信息

通讯作者:
王效民,Email:wxm@xmzsh.com

中图分类号: R617
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- 被引次数: 0
出版历程
- 收稿日期: 2014-05-18
- 刊出日期: 2014-09-15

Comparison on liver transplantation rejection among various strains combination of rats

1.
Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen 361004, China

摘要

摘要: 目的比较不同品系大鼠之间肝移植排斥反应特点。方法依据大鼠不同品系分成对照组SD→SD(A组),实验组Wistar→SD(B组)、Lewis→BN(C组)以及DA→Lewis(D组)4个组,采用Kamada双袖套法建立大鼠原位肝移植模型。比较各组受体大鼠术后10 d血清肝功能指标[丙氨酸转氨酶(ALT)、总胆红素(TB)和白蛋白(Alb)]、血清白细胞介素(IL)-2和IL-10水平、急性排斥反应组织病理学分级和术后平均生存时间。结果与A、B组比较,C组和D组的血清ALT和TB明显升高,Alb明显降低,差异均有统计学意义(均为P<0.05)。与C组比较,D组的TB明显升高,Alb明显降低,差异均有统计学意义(均为P<0.05)。与A组比较,B、C、D组大鼠血清IL-2和IL-10水平均明显升高,C组和D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。与B组比较,C组和D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。与C组比较,D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。肝组织病理学检查显示,A组大鼠肝组织未见明显排斥反应,排斥活动性指数(RAI)评分(1.8±0.7)分;B组RAI评分(3.1±1.3)分,属轻度或不明确性排斥反应;C组RAI评分(6.9±0.8)分,属中~重度排斥反应;D组RAI评分(8.8±0.5)分,属重度排斥反应。各组间RAI评分比较以及组间两两比较,差异均有统计学意义(均为P<0.05)。A组、B组、C组、D组受体大鼠术后平均生存时间分别为(119.3±1.9)d、(116.9±8.3)d、(53.4±6.1)d、(12.1±2.4)d,A组与B组的生存时间比较差异无统计学意义,余各组两两比较差异均有统计学意义(均为P<0.05)。结论 4种组合中,大鼠DA→Lewis模型排斥反应最剧烈,Lewis→BN次之,而Wistar→SD最轻,接近于免疫耐受。
- 肝移植 /
- 排斥反应 /
- 模型 /
- 大鼠 /
- 白细胞介素
Abstract: Objective To compare the rejection of liver transplantation in different strains combination of rats. Methods Four transplantation models of various strain combinations were established including the control group SD (donor) to SD (recipient) (group A) and the experimental groups Wistar to SD(group B), Lewis to BN(group C) and DA to Lewis(group D). Orthotopic liver transplantation model of rats were constructed by Kamada's two cuff technique. And serum hepatic functions in 4 groups of recipient rats at 10^th day after liver transplantation were compared, which was including alanine aminotransferase (ALT), total bilirubin (TB) and albumin (Alb). Meanwhile the serum levels of interleukin(IL)-2 and IL-10, rejection activity index(RAI) at 10^th day after liver transplantation and the average survival time of recipient rats were investigated. Results Compared with group A and B, the serum levels of ALT and TB of group C and D increased obviously, while Alb decreased significantly. Compared with group C, TB of group D increased obviously, while Alb decreased remarkably. All of the differences were statistically significant (all in P<0.05). Compared with group A, the serum levels of IL-2 and IL-10 in group B, C and D all elevated significantly, and IL-2/IL-10 in group C and D increased remarkably too (all in P<0.05). Compared with group B, IL-2 in group C and D increased significantly, and IL-2/IL-10 in group D also elevated significantly. Compared with group C, both IL-2 and IL-2/IL-10 in group D increased significantly. All the differences were statistically significant (all in P<0.05). Hepatic histopathological examination showed that obvious rejection did not occur in the recipient rats of group A, which rejection activity index (RAI) was scored 1.8±0.7. The RAI score of Group B,C and D were 3.1±1.3, 6.9±0.8 and 8.8±0.5, which belonged to mild or vague rejection, moderate to severe rejection and severe rejection respectively. All the RAI scores comparison among and between each group had statistical differences (all in P<0.05). The average survival time of recipient rats in group A, B, C and D were (119.3±1.9) d, (116.9±8.3) d, (53.4±6.1) d and (12.1±2.4) d respectively. There was no statistically significant difference between group A and B, while the comparison between any other group was statistically significant (all in P<0.05). Conclusion In four different rats strains combination, the rejection is most serious in the model of DA (donor) to Lewis (recipient), moderate in Lewis to BN, mildest and near to tolerance in Wistar to SD.
- Liver transplantation /
- Rejection /
- Model /
- Rat /
- Interleukin

HTML全文

图 1 各组受体大鼠肝组织病理切片（HE，×200）

注：A、B、C、D图分别为A、B、C、D组受体大鼠肝移植术后10 d肝组织病理切片

Figure 1. Pathological sections of liver tissue of recipient rats in4 groups

下载: 全尺寸图片幻灯片

表 1 各组受体大鼠肝移植术后10 d 血清肝功能指标的比较

Table 1. Comparison of the indexes of hepatic function of recipient rats among4 groups at10th day after liver transplantation(x±s)

组别	n	ALT（U/L）	TB（μmol/L）	Alb（g/L）
A组	8	89±7	8±2	44±2
B组	8	91±11	9±2	43±2
C组	8	401±18^a,b	97±16^a,b	24±1^a,b
D组	8	416±22^a,b	163±19^a,b,c	14±2^a,b,c
注：与A组比较，^aP＜0.05；与B组比较，^bP＜0.05；与C组比较，cP＜0.05

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表 2 各组受体大鼠肝移植术后10 d血清IL-2和IL-10水平的比较

Table 2. Comparison of the serum levels of IL-2 and IL-10 of recipient rats among4 groups at10th day after liver transplantation(x±s)

组别	n	IL-2(μg/L)	IL-10(μg/L)	IL-2 / IL-10
A组	8	25.6±2.6	114±13	0.22±0.03
B组	8	43.8±5.2^a	172±25^a	0.26±0.03
C组	8	201.5±7.3^a,b	168±28^a	1.23±0.22^a
D组	8	397.0±11.3^a,b,c	158±31^a	2.60±0.50^a,b,c
注：与A组比较，^aP＜0.05；与B组比较，^bP＜0.05；与C组比较，cP＜0.05

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参考文献(17)

[1]	Kamada N, Calne RY. Orthotopic liver transplantation in the rat. technique using cuff for portal vein anastomosis and biliary drainage[J]. Transplantation,1979,28(1):47-50. doi: 10.1097/00007890-197907000-00011
[2]	Banff schema for grading liver allograft rejection: an international consensus document[J]. Hepatology,1997,25(3):658-663. http://www.oalib.com/references/10875543
[3]	Tu Y, Arima T, Flye MW. Rejection of spontaneously accepted rat liver allografts with recipient interleukin-2 treatment or donor irradiation[J]. Transplantation,1997,63(2):177-181. doi: 10.1097/00007890-199701270-00001
[4]	Kiyomoto T, Ito T, Uchikoshi F, et al. The potent role of graft-derived NKR-P1⁺ TCRalphabeta⁺ T (NKT) cells in the spontaneous acceptance of rat liver allografts[J]. Transplantation,2005,80(12):1749-1755. doi: 10.1097/01.tp.0000185306.40150.28
[5]	Chiang KC, Ohmori N, Goto T. The search for immunosuppressive therapies to induce tolerance in organ transplantation[J]. Endocr Metab Immune Disord Drug Targets,2011,11(2):173-180. doi: 10.2174/187153011795564197
[6]	Toyokawa H, Nakao A, Bailey RJ, et al. Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation[J]. Liver Transpl,2008,14(3):346-357. doi: 10.1002/lt.v14:3
[7]	Dresske B, Lin X, Huang DS, et al. Spontaneous tolerance: experience with the rat liver transplant model[J]. Hum Immunol,2002,63(10):853-861. doi: 10.1016/S0198-8859(02)00448-2
[8]	Yamamoto S, Okuda T, Yamasaki K, et al. FK778 and FK506 combination therapy to control acute rejection after rat liver allotransplantation[J]. Transplantation,2004,78(11):1618-1625. doi: 10.1097/01.TP.0000144312.08782.16
[9]	Feng JF, Chen F, Liu H, et al. Induction of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation[J]. Minerva Chir,2013,68(2):183-189. http://cn.bing.com/academic/profile?id=2413760676&encoded=0&v=paper_preview&mkt=zh-cn
[10]	Liang S, Chen Y, Long F, et al. Correlation between augmenter of liver regeneration and IFN-γ expression in graft after rat orthotopic liver transplantation[J]. J Surg Res,2012,178(2):968-973. doi: 10.1016/j.jss.2012.06.032
[11]	Wang GY, Zhang Q, Yang Y, et al. Rapamycin combined with allogenic immature dendritic cells selectively expands CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in rats[J]. Hepatobiliary Pancreat Dis Int,2012,11(2):203-208. doi: 10.1016/S1499-3872(12)60149-0
[12]	Jiang Z, Chen Y, Feng X, et al. Hepatic stellate cells promote immunotolerance following orthotopic liver transplantation in rats via induction of T cell apoptosis and regulation of Th2/Th3-like cell cytokine production[J]. Exp Ther Med,2013,5(1):165-169. http://cn.bing.com/academic/profile?id=2026288271&encoded=0&v=paper_preview&mkt=zh-cn
[13]	Lin SZ, Chen KJ, Tong HF, et al. Emodin attenuates acute rejection of liver allografts by inhibiting hepatocellular apoptosis and modulating the Th1/Th2 balance in rats[J]. Clin Exp Pharmacol Physiol,2010,37(8):790-794. http://cn.bing.com/academic/profile?id=1986660693&encoded=0&v=paper_preview&mkt=zh-cn
[14]	Yang ZL, Cheng K, Sun HG, et al. Changes in peripheral blood Th1 and Th2 cells in rat liver transplantation under different immune statuses[J]. Genet Mol Res,2013,12(4):6939-6946. doi: 10.4238/2013.December.19.13
[15]	Li T, Zhao JM, Zhang Y, et al. Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis[J]. Chin Med J, 2011,124(18):2818-2823. http://cn.bing.com/academic/profile?id=2399884314&encoded=0&v=paper_preview&mkt=zh-cn
[16]	张剑,张琪,汪国营,等.T细胞分化群40补体免疫球蛋白基因修饰骨髓间充质干细胞在肝移植排斥反应中的作用[J].南方医科大学学报,2011,31(11):1903-1906. http://www.cnki.com.cn/Article/CJFDTOTAL-DYJD201111024.htm Zhang J, Zhang Q, Wang GY, et al. Effects of CD40LIg gene-modified bone marrow mesenchymal stem cells on liver graft rejection in rats[J]. J South Med Univ,2011,31(11):1903-1906. http://www.cnki.com.cn/Article/CJFDTOTAL-DYJD201111024.htm
[17]	Kunugi S, Shimizu A, Ishii E, et al. The pathological characteristics of acute antibody-mediated rejection in DA-to-Lewis rat orthotopic liver transplantation[J]. Transplant Proc,2011,43(7):2737-2740. doi: 10.1016/j.transproceed.2011.04.024