他克莫司对二乙基亚硝胺诱导肝细胞癌模型大鼠原位肝移植术后急性排斥反应的实验研究  

Experimental study of tacrolimus on acute rejection after orthotopic liver transplantation in hepatocellular carcinoma rat model induced by two ethyl nitrite

作　　者：邓卫平 马德强 郑红梅 李胜保 郜元军 金曙 

机构地区：[1]十堰市太和医院(湖北医药学院附属医院)消化内科,湖北十堰442000 [2]十堰市太和医院(湖北医药学院附属医院)肝病中心,湖北十堰442000 [3]十堰市太和医院(湖北医药学院附属医院)技能培训中心,湖北十堰442000

出　　处：《临床和实验医学杂志》2018年第1期9-12,共4页Journal of Clinical and Experimental Medicine

基　　金：湖北省教育厅科研项目(编号:B2016125)

摘　　要：目的观察他克莫司对二乙基亚硝胺诱导同种肝细胞癌模型大鼠原位肝移植术后急性排斥反应的影响。方法雄性Lewis大鼠66只,选取其中16只设为空白对照组,再选取其中50只大鼠为受体。采用二乙基亚硝胺灌胃诱导受体大鼠肝癌模型,成模后用改良双袖套法将40只正常供体DA大鼠肝脏移植于受体。术后随机分为模型对照组和他克莫司组。术后他克莫司组用他克莫司1.0 mg(kg·d)混悬液灌胃,空白对照组和模型对照组按1.0 mg/(kg·d)灌生理盐水。采用酶联免疫法(ELISA)于2周和4周检测肝组织白介素-2(IL-2)、IL-4、IL-12、干扰素-γ(IFN-γ)、肿瘤坏死因子α(TNF-α)及转化生长因子β1(TGF-β1);流式细胞仪检测T淋巴细胞亚群T细胞(Treg)、CD4^+T细胞和CD8^+T细胞占T淋巴细胞的比率。结果与空白对照组比较,模型对照组在2周和4周IL-2、IL-4、IL-12、IFN-γ、TGF-β1、TNF-α、CD4^+T%、CD8^+T%均明显升高,差异均有统计学意义(P<0.05);与模型对照组比较,他克莫司组在2周和4周IL-2、IL-4、IL-12、IFN-γ、TGF-β1、TNF-α、CD4^+T%、CD8^+T%均明显降低,差异均有统计学意义(P<0.05);且他克莫司组2周时与模型对照组比较各指标明显降低(P<0.05);4周时与同组治疗2周比较各指标明显降低(P<0.05)。结论他克莫司可降低二乙基亚硝胺诱导肝细胞癌模型大鼠原位肝移植术后急性排斥反应,具有明显的免疫抑制作用。Objective To observe the effect of tacrolimus on acute rejection after orthotopic liver transplantation in hepatocellular carcino-ma rat model induced by two ethyl nitrite. Methods 66 male Lewis rats were selected,and 16 of them were set to blank control group,and then 50 rats were selected as receptors which were gavaged and induced by diethylnitrosamine induced to make liver cancer rat model. After modeling, modified double cuff method was used to transplant donor livers of 40 normal DA rats on receptors,after the surgery,they were randomly divided into model group and tacrolimus group. Tacrolimus 1. 0 mg/（kg·d）suspension was used to fill the stomaches of tacrolimus group,the control group and the model group were injected with physiological saline [1. 0 mg/（kg·d）]. ELISA was used in 2 and 4 weeks to detect interleukin -2 （Interleukin - 2,IL - 2）,IL - 4,IL - 12,interferon gamma - γ （IFN - γ）,tumor necrosis factor （TNF - α）and transforming growth factor- β1 （TGF - β1）of the liver tissue;flow cytometry was used to detect T lymphocyte subsets and the percentage of T cells （Treg）accounted for the T lymph cell （Treg%）,the proportion of CD4 ＋ T cells and CD8 ＋ T cells accounted for T lymphocytes （%）. Results Compared with the blank control group,IL - 2,IL - 4,IL - 12,IFN - γ,TGF - β1,TNF - α,CD4 ＋ T% and CD8 ＋ T% were significantly increased in the model control group in 2 and 4 weeks,the difference was statistically significant （P 〈 0. 05）;Compared with the model control group,IL - 2,IL - 4, IL - 12,IFN - γ,TNF - α,TGF - β1,CD4 ＋ T%,CD8 ＋ T% were significantly lower in the tacrolimus group at 2 and 4 weeks （P 〈 0. 05）. The tacrolimus group was compared with the model control group at 2 weeks （P 〈 0. 05）,and compared with the same treatment group at 4 weeks and 2 weeks （P 〈 0. 05）. Conclusion Tacrolimus can reduce the acute rejection after orthotopic liver transplantation in hepatocellular carcino-ma of the rat model induced by two e

关 键 词：大鼠 肝细胞癌 原位肝脏移植 他克莫司 急性排斥反应 

分 类 号：R-332[医药卫生] R735.7