發(fā)布時間：2018-06-13 05:21

  本文選題：失代償期肝硬化 + 間充質(zhì)干細胞��； 參考：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：目的探討人臍帶間充質(zhì)干細胞(Human umbilical cord mesenchymal stem cells,h UC-MSCs)移植治療后失代償期乙型肝炎肝硬化患者體內(nèi)免疫狀態(tài)的變化以及對于患者預后的影響。方法將符合選擇標準的失代償期乙型肝炎肝硬化患者(118例)隨機分為2組,所有患者均行內(nèi)科綜合治療,而h UC-MSCs治療組(觀察組)除了內(nèi)科綜合治療外,另外給予人臍帶間充質(zhì)干細胞移植,即在入院后1周內(nèi)在介入條件下(經(jīng)肝固有動脈)緩慢注射預先備好的干細胞懸液20ml,細胞總數(shù)為(4.0~4.5)×108。于治療前、治療后1、4周,運用Elisa法檢測血清白細胞介素6(IL-6)、腫瘤壞死因子α(TNF-α)、白細胞介素10(IL-10)和轉(zhuǎn)化生長因子β(TGF-β)的水平,并且使用流式細胞儀測定患者外周血淋巴細胞亞群的分布比例;于治療后4,8,12,24,36和48周,檢測兩組MELD評分、Child-Pugh分級變化;隨訪觀察肝衰竭、并發(fā)癥及生存情況。結(jié)果觀察組治療后1,4周的血清白細胞介素6、腫瘤壞死因子α水平明顯低于對照組(P0.05或P0.001),白細胞介素10(IL-10)、轉(zhuǎn)化生長因子β(TGF-β)水平明顯高于對照組(P0.05或P0.001);觀察組治療后1周的CD3+CD4+T細胞、CD4+CD25+Treg細胞比例高于對照組(P0.001),CD3+CD8+T細胞、CD3-CD19+B細胞低于對照組(P0.05或P0.001);治療后4周的CD3+T細胞、CD3+CD4+T細胞、CD4+CD25+Treg細胞比例高于對照組(P0.05或P0.001),CD3+CD8+T細胞、CD3-CD19+B細胞低于對照組(P0.05或P0.001);治療后4,8,12,24周細胞治療組的MELD評分和Child-Pugh分級均低于對照組(P0.05);觀察期間,h UC-MSCs組無患者發(fā)生肝衰竭,而對照組則有5例發(fā)生肝衰竭;h UC-MSCs組并發(fā)癥的發(fā)生率顯著低于對照組(P0.05);隨訪52周,h UC-MSCs組的累計死亡率顯著低于對照組(P0.05)。結(jié)論人臍帶間充質(zhì)干細胞移植治療失代償期乙型肝炎肝硬化患者后,可能通過旁分泌的機制調(diào)節(jié)患者體內(nèi)的免疫炎癥反應(yīng),抑制或減輕肝組織內(nèi)局部炎癥,顯著改善肝功能,尤其以短期療效為主,以及降低患者的肝衰竭發(fā)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 鹵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- 偽, 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 偽, 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.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R512.62;R575.2

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