本文選題：兒童肝移植 + 排斥反應(yīng)　； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究目的:研究膽道閉鎖兒童肝移植患者外周血中CD4+CD25+Foxp3+調(diào)節(jié)性T細(xì)胞(Regulatory T cells,Treg)與輔助性T細(xì)胞17(T helper cell 17,Th17)的表達(dá),分析其臨床意義。研究方法:納入自2016年6月至2017年4月期間于天津市第一中心醫(yī)院小兒肝臟移植科就診的肝移植手術(shù)后隨訪患兒以及初次接受肝移植手術(shù)的患兒42例,原發(fā)病均為膽道閉鎖。其中初次接受肝移植手術(shù)治療的患兒12例作為肝移植手術(shù)觀察組,分別于肝移植術(shù)前、術(shù)后2周及術(shù)后1月留取外周靜脈血樣。肝移植術(shù)后超過1年,臨床狀態(tài)穩(wěn)定的肝移植術(shù)后患兒19例作為肝移植長期存活組;根據(jù)免疫抑制劑他克莫司(Tacrolimus,FK506)血藥濃度不同,分為低濃度組(FK5064.0ng/ml)和高濃度組(FK506≥4.0ng/ml)。肝移植術(shù)后發(fā)生排斥反應(yīng)的患兒11例作為肝移植排斥組,并分別在抗排斥治療前后留取外周靜脈血樣。另外納入健康兒童10例作為健康對照組。將靜脈血樣標(biāo)記相應(yīng)熒光結(jié)合抗體后,應(yīng)用流式細(xì)胞儀檢測Treg細(xì)胞與Th17細(xì)胞以及細(xì)胞毒性T細(xì)胞(Cytotoxic T cell,CTL)的表達(dá)情況。分別比較各組Treg細(xì)胞和Th17細(xì)胞比例的變化情況,分析其意義。研究結(jié)果:肝移植手術(shù)觀察組中,肝移植術(shù)前及術(shù)后不同時間點(diǎn)Treg細(xì)胞比例均低于健康組(P0.05)。術(shù)前Treg細(xì)胞比例高于術(shù)后2周(P=0.000)及術(shù)后1月(P=0.000),而術(shù)后2周與術(shù)后1月Treg細(xì)胞比例差異無統(tǒng)計學(xué)意義(P=0.475)。肝移植術(shù)后各時間點(diǎn)Th17細(xì)胞比例均高于健康組(P0.05)。手術(shù)前后不同時間點(diǎn)的Th17細(xì)胞比例差異無統(tǒng)計學(xué)意義(P=0.119)。肝移植長期存活組中,可見肝移植長期存活組患兒Treg細(xì)胞比例低于健康兒童(P=0.021)。而肝移植術(shù)后1年患兒與肝移植術(shù)后2年患兒之間Treg細(xì)胞比例差異無統(tǒng)計學(xué)意義(P=0.077)。肝移植術(shù)后長期存活組患兒Th17細(xì)胞比例高于健康組(P=0.008)。兒童肝移植術(shù)后2年患兒Th17細(xì)胞比例低于術(shù)后1年患者(P=0.028)。FK506高濃度組和低濃度組Treg細(xì)胞比例均低于健康組,(P0.05)。而FK506高濃度組與低濃度組相比,Treg細(xì)胞比例差異無統(tǒng)計學(xué)意義(P=0.876)。Treg細(xì)胞比例與FK506濃度無直線相關(guān)關(guān)系(P=0.611)。FK506高濃度組和低濃度組Th17細(xì)胞比例均高于健康組(P0.05)。而FK506高濃度組與低濃度組相比,Th17細(xì)胞比例差異無統(tǒng)計學(xué)意義(P=0.396)。Th17細(xì)胞比例與FK506濃度無直線相關(guān)關(guān)系(P=0.729)。在肝移植排斥組中,抗排斥治療前肝移植患兒Treg細(xì)胞比例低于健康組(P=0.000)及肝移植穩(wěn)定組(P=0.000)。而抗排斥治療后肝移植患兒Treg細(xì)胞比例低于抗排斥治療前(P=0.001)。肝移植排斥組患兒抗排斥治療前Th17細(xì)胞比例高于健康組(P=0.000)及肝移植穩(wěn)定組(P=0.000)�？古懦庵委熀骉h17細(xì)胞比例低于抗排斥治療前(P=0.000)。肝移植穩(wěn)定組患兒CTL細(xì)胞比例高于健康組(P=0.015)。肝移植排斥組患兒抗排斥治療前CTL細(xì)胞比例高于健康組(P=0.000)及肝移植穩(wěn)定組(P=0.000)�？古懦庵委熀驝TL細(xì)胞比例低于抗排斥治療前(P=0.001)。研究結(jié)論:(1)膽道閉鎖肝移植患兒術(shù)前及術(shù)后早期Treg細(xì)胞比例均低于健康兒童。Treg細(xì)胞比例在術(shù)后早期(術(shù)后1月)呈下降趨勢。術(shù)后早期Th17細(xì)胞比例均高于健康組,變化不明顯。(2)FK506對Treg細(xì)胞比例具有較強(qiáng)抑制作用,而對Th17細(xì)胞比例抑制作用較弱。FK506對Treg細(xì)胞比例及Th17細(xì)胞比例的影響與FK506濃度無關(guān)。(3)膽道閉鎖而肝移植術(shù)后發(fā)生排斥反應(yīng)時,外周血Treg細(xì)胞比例下降,而Th17細(xì)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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R726.5

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