Treg与Th17在胆道闭锁儿童肝移植患者外周血中的表达及意义

发布时间：2018-06-18 20:35

本文选题：儿童肝移植 + 排斥反应　；参考：《天津医科大学》2017年硕士论文

【摘要】：研究目的:研究胆道闭锁儿童肝移植患者外周血中CD4+CD25+Foxp3+调节性T细胞(Regulatory T cells,Treg)与辅助性T细胞17(T helper cell 17,Th17)的表达,分析其临床意义。研究方法:纳入自2016年6月至2017年4月期间于天津市第一中心医院小儿肝脏移植科就诊的肝移植手术后随访患儿以及初次接受肝移植手术的患儿42例,原发病均为胆道闭锁。其中初次接受肝移植手术治疗的患儿12例作为肝移植手术观察组,分别于肝移植术前、术后2周及术后1月留取外周静脉血样。肝移植术后超过1年,临床状态稳定的肝移植术后患儿19例作为肝移植长期存活组;根据免疫抑制剂他克莫司(Tacrolimus,FK506)血药浓度不同,分为低浓度组(FK5064.0ng/ml)和高浓度组(FK506≥4.0ng/ml)。肝移植术后发生排斥反应的患儿11例作为肝移植排斥组,并分别在抗排斥治疗前后留取外周静脉血样。另外纳入健康儿童10例作为健康对照组。将静脉血样标记相应荧光结合抗体后,应用流式细胞仪检测Treg细胞与Th17细胞以及细胞毒性T细胞(Cytotoxic T cell,CTL)的表达情况。分别比较各组Treg细胞和Th17细胞比例的变化情况,分析其意义。研究结果:肝移植手术观察组中,肝移植术前及术后不同时间点Treg细胞比例均低于健康组(P0.05)。术前Treg细胞比例高于术后2周(P=0.000)及术后1月(P=0.000),而术后2周与术后1月Treg细胞比例差异无统计学意义(P=0.475)。肝移植术后各时间点Th17细胞比例均高于健康组(P0.05)。手术前后不同时间点的Th17细胞比例差异无统计学意义(P=0.119)。肝移植长期存活组中,可见肝移植长期存活组患儿Treg细胞比例低于健康儿童(P=0.021)。而肝移植术后1年患儿与肝移植术后2年患儿之间Treg细胞比例差异无统计学意义(P=0.077)。肝移植术后长期存活组患儿Th17细胞比例高于健康组(P=0.008)。儿童肝移植术后2年患儿Th17细胞比例低于术后1年患者(P=0.028)。FK506高浓度组和低浓度组Treg细胞比例均低于健康组,(P0.05)。而FK506高浓度组与低浓度组相比,Treg细胞比例差异无统计学意义(P=0.876)。Treg细胞比例与FK506浓度无直线相关关系(P=0.611)。FK506高浓度组和低浓度组Th17细胞比例均高于健康组(P0.05)。而FK506高浓度组与低浓度组相比,Th17细胞比例差异无统计学意义(P=0.396)。Th17细胞比例与FK506浓度无直线相关关系(P=0.729)。在肝移植排斥组中,抗排斥治疗前肝移植患儿Treg细胞比例低于健康组(P=0.000)及肝移植稳定组(P=0.000)。而抗排斥治疗后肝移植患儿Treg细胞比例低于抗排斥治疗前(P=0.001)。肝移植排斥组患儿抗排斥治疗前Th17细胞比例高于健康组(P=0.000)及肝移植稳定组(P=0.000)。抗排斥治疗后Th17细胞比例低于抗排斥治疗前(P=0.000)。肝移植稳定组患儿CTL细胞比例高于健康组(P=0.015)。肝移植排斥组患儿抗排斥治疗前CTL细胞比例高于健康组(P=0.000)及肝移植稳定组(P=0.000)。抗排斥治疗后CTL细胞比例低于抗排斥治疗前(P=0.001)。研究结论:(1)胆道闭锁肝移植患儿术前及术后早期Treg细胞比例均低于健康儿童。Treg细胞比例在术后早期(术后1月)呈下降趋势。术后早期Th17细胞比例均高于健康组,变化不明显。(2)FK506对Treg细胞比例具有较强抑制作用,而对Th17细胞比例抑制作用较弱。FK506对Treg细胞比例及Th17细胞比例的影响与FK506浓度无关。(3)胆道闭锁而肝移植术后发生排斥反应时,外周血Treg细胞比例下降,而Th17细胞比例升高。
[Abstract]:Objective: To study the expression of CD4+CD25+Foxp3+ regulatory T cells (Regulatory T cells, Treg) and auxiliary T cell 17 (T helper cell 17, Th17) in peripheral blood of children with biliary atresia, and to analyze its clinical significance. The study methods were included from June 2016 to April 2017 in the pediatric liver transplantation in Tianjin First Central Hospital 42 children were followed up after liver transplantation as well as 42 children who received liver transplantation for the first time. The primary disease was biliary atresia. 12 of the first patients received liver transplantation as the observation group of liver transplantation, before the liver transplantation, 2 weeks after the operation and in January after the operation. More than 1 after liver transplantation. 19 children with stable liver transplantation were used as long-term survival group after liver transplantation. According to the different concentrations of Tacrolimus (FK506), they were divided into low concentration group (FK5064.0ng/ml) and high concentration group (FK506 > 4.0ng/ml). After liver transplantation, 11 cases of rejection in the liver transplant rejection group were divided into the liver transplantation rejection group. In addition to 10 healthy children as a healthy control group, 10 healthy children were taken as a healthy control group. The expression of Treg cells and Th17 cells and cytotoxic T cells (Cytotoxic T cell, CTL) were detected by flow cytometry. Treg cells and Th1 in each group were compared. The change of the proportion of 7 cells was analyzed. The results were as follows: the proportion of Treg cells before and after liver transplantation was lower than that in the healthy group (P0.05). The proportion of Treg cells before the operation was higher than that of 2 weeks after the operation (P=0.000) and after the operation in January (P=0.000), but there was no difference between the 2 weeks after the operation and the proportion of Treg cells in the postoperative period after the operation. Significance (P=0.475). The proportion of Th17 cells at all time points after liver transplantation was higher than that of the healthy group (P0.05). There was no significant difference in the proportion of Th17 cells at different time points before and after the operation (P=0.119). In the long-term survival group of liver transplantation, the proportion of Treg cells in the long-term survival group of liver transplantation was lower than that of healthy children (P=0.021). And 1 years after liver transplantation There was no significant difference in the proportion of Treg cells between children and children after 2 years of liver transplantation (P=0.077). The proportion of Th17 cells in the long-term survival group after liver transplantation was higher than that of the healthy group (P=0.008). The proportion of Th17 cells in children 2 years after liver transplantation was lower than that of the 1 years after the operation (P=0.028), the proportion of Treg cells in the high concentration group and the low concentration group was low. In the healthy group, (P0.05), the proportion of Treg cells in the high concentration group of FK506 was not statistically significant (P=0.876) and there was no linear correlation between the proportion of.Treg cells and the concentration of FK506 (P=0.611), the proportion of Th17 cells in the high concentration group and the low concentration group were higher than that in the healthy group (P0.05). The FK506 high concentration group was smaller than the low concentration group, and the Th17 thin was fine. There was no significant difference in the proportion of cell ratio (P=0.396).Th17 cell ratio and FK506 concentration (P=0.729). In the liver transplant rejection group, the proportion of Treg cells in the children with liver transplantation before the rejection treatment was lower than that of the healthy group (P=0.000) and the liver transplantation stable group (P=0.000). The proportion of Treg cells in the children with liver transplantation after the anti rejection treatment was lower than that of the anti rejection group. Before treatment (P=0.001). The proportion of Th17 cells before the treatment of rejection in the liver transplantation rejection group was higher than that in the healthy group (P=0.000) and the liver transplantation stable group (P=0.000). The proportion of Th17 cells after anti rejection treatment was lower than before the anti rejection treatment (P=0.000). The CTL cell ratio of the children with the liver transplantation stability group was higher than that of the healthy group (P=0.015). The anti rejection group of the liver transplantation rejection group was resistant to rejection. The proportion of CTL cells before the treatment was higher than that in the healthy group (P=0.000) and the stable liver transplantation group (P=0.000). The proportion of CTL cells after anti rejection treatment was lower than before the anti rejection treatment (P=0.001). (1) the proportion of Treg cells before and after the biliary atresia transplantation was lower than the proportion of.Treg cells in healthy children before and after the operation (January after the operation). The proportion of Th17 cells in early postoperative period was higher than that in the healthy group. (2) FK506 had a strong inhibitory effect on the proportion of Treg cells, while the effect of.FK506 on the proportion of Treg cells and the ratio of Th17 cells to the proportion of Treg cells was not related to the concentration of FK506. (3) the biliary atresia and the rejection of the liver transplantation after the liver transplantation. The proportion of Treg cells in peripheral blood decreased, while the proportion of Th17 cells increased.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R726.5

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