人脐带间充质干细胞治疗后失代偿期乙型肝炎肝硬化患者的免疫功能和预后

发布时间：2018-06-13 05:21

本文选题：失代偿期肝硬化 + 间充质干细胞　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的探讨人脐带间充质干细胞(Human umbilical cord mesenchymal stem cells,h UC-MSCs)移植治疗后失代偿期乙型肝炎肝硬化患者体内免疫状态的变化以及对于患者预后的影响。方法将符合选择标准的失代偿期乙型肝炎肝硬化患者(118例)随机分为2组,所有患者均行内科综合治疗,而h UC-MSCs治疗组(观察组)除了内科综合治疗外,另外给予人脐带间充质干细胞移植,即在入院后1周内在介入条件下(经肝固有动脉)缓慢注射预先备好的干细胞悬液20ml,细胞总数为(4.0~4.5)×108。于治疗前、治疗后1、4周,运用Elisa法检测血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)和转化生长因子β(TGF-β)的水平,并且使用流式细胞仪测定患者外周血淋巴细胞亚群的分布比例;于治疗后4,8,12,24,36和48周,检测两组MELD评分、Child-Pugh分级变化;随访观察肝衰竭、并发症及生存情况。结果观察组治疗后1,4周的血清白细胞介素6、肿瘤坏死因子α水平明显低于对照组(P0.05或P0.001),白细胞介素10(IL-10)、转化生长因子β(TGF-β)水平明显高于对照组(P0.05或P0.001);观察组治疗后1周的CD3+CD4+T细胞、CD4+CD25+Treg细胞比例高于对照组(P0.001),CD3+CD8+T细胞、CD3-CD19+B细胞低于对照组(P0.05或P0.001);治疗后4周的CD3+T细胞、CD3+CD4+T细胞、CD4+CD25+Treg细胞比例高于对照组(P0.05或P0.001),CD3+CD8+T细胞、CD3-CD19+B细胞低于对照组(P0.05或P0.001);治疗后4,8,12,24周细胞治疗组的MELD评分和Child-Pugh分级均低于对照组(P0.05);观察期间,h UC-MSCs组无患者发生肝衰竭,而对照组则有5例发生肝衰竭;h UC-MSCs组并发症的发生率显著低于对照组(P0.05);随访52周,h UC-MSCs组的累计死亡率显著低于对照组(P0.05)。结论人脐带间充质干细胞移植治疗失代偿期乙型肝炎肝硬化患者后,可能通过旁分泌的机制调节患者体内的免疫炎症反应,抑制或减轻肝组织内局部炎症,显著改善肝功能,尤其以短期疗效为主,以及降低患者的肝衰竭发生率和死亡率。
[Abstract]:Objective to investigate the changes of immune status and prognosis of patients with decompensated hepatitis B cirrhosis after transplantation of human umbilical cord mesenchymal stem cells with human umbilical cord mesenchymal stem cells. Methods 118 patients with decompensated hepatitis B cirrhosis who met the selection criteria were randomly divided into two groups. All patients were treated with comprehensive medical therapy, while the observation group (observation group) was treated with hUC-MSCs in addition to comprehensive medical therapy. In addition, human umbilical cord mesenchymal stem cells were transplanted, that is, 20 ml stem cell suspension was slowly injected under interventional condition (via the proper hepatic artery) within 1 week after admission, the total number of cells was 4.0 卤4.5) 脳 10 8 脳 10 ~ (8) 脳 10 ~ (8) 脳 10 ~ (8) 脳 10 ~ (8) 脳 10 ~ (8). Serum levels of interleukin-6, TNF- 伪, IL-10, TGF- 尾 and TGF- 尾 were detected by Elisa before and 1 to 4 weeks after treatment. The distribution ratio of lymphocyte subsets in peripheral blood was measured by flow cytometry, and the meld scores and Child-Pugh grades were detected at the end of 4 weeks after treatment, and the liver failure, complications and survival were observed. Results the levels of serum interleukin 6, tumor necrosis factor 伪, interleukin 10 and transforming growth factor 尾 TGF- 尾 in the observation group were significantly lower than those in the control group (P 0.05 or P 0.001), and the levels of IL-10 and TGF- 尾 were significantly higher in the observation group than those in the control group (P 0.05 or P 0.001), and the levels of TGF- 尾 in the observation group were significantly higher than those in the control group (P 0.05 or P 0.001). The percentage of CD4 CD25 Treg cells in CD3 CD4 T cells was higher than that in control group (P 0.001), and the percentage of CD3-CD19 B cells was lower than that of control group (P 0.05 or P 0.001), and the percentage of CD3 CD4 T cells and CD3 CD25 T cells was higher than that of control group (P 0.05 or P 0.001CD 3 CD 3 CD 8 T cells) at 4 weeks after treatment, and the ratio of CD 3 CD 3 T cells to CD 4 T cells in the control group was higher than that in the control group. CD3-CD19B cells were lower than those of control group (P0.05 or P0.001), the meld score and Child-Pugh grade of 24 weeks treatment group were lower than those of control group (P 0.05), and no liver failure occurred in UC-MSCs group during the observation period. In the control group, the incidence of complications in the UC-MSCs group was significantly lower than that in the control group (P 0.05), and the cumulative mortality in the UC-MSCs group was significantly lower than that in the control group after 52 weeks of follow-up. Conclusion after transplantation of human umbilical cord mesenchymal stem cells in patients with decompensated hepatitis B cirrhosis, the immune inflammatory response of patients may be regulated by paracrine mechanism, local inflammation in liver tissue can be inhibited or alleviated, and liver function can be significantly improved. In particular, short-term efficacy is the main treatment, and reduce the incidence of liver failure and mortality.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R575.2

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