本文選題：MSC + 間充質(zhì)干細(xì)胞��； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:長期的免疫抑制會顯著提高移植受者發(fā)生惡性腫瘤和感染性疾病的概率,免疫抑制劑無法防止或者延遲慢性移植物排斥反應(yīng)的發(fā)生。近年來相繼有多篇文獻(xiàn)報(bào)道間充質(zhì)干細(xì)胞(MSC)具有免疫調(diào)節(jié)作用,能夠誘導(dǎo)穩(wěn)定的免疫耐受狀態(tài)的產(chǎn)生,從而有利于降低移植免疫排斥的發(fā)生率。本實(shí)驗(yàn)將通過比較肝移植術(shù)后聯(lián)合huc-MSC治療患者和只接受常規(guī)免疫抑制劑治療肝移植的患者的免疫指標(biāo)、不良事件(Treatment-emergent adverse events,TEAE)發(fā)生率、相關(guān)并發(fā)癥發(fā)生率、移植后肝功能的比較,來評估huc-MSC臨床應(yīng)用的安全性和可行性。方法:將2014年7月至2015年11月在解放軍81醫(yī)院肝臟移植中心實(shí)施同種異體肝移植的總計(jì)40例患者經(jīng)1:1的比例按入組時(shí)間隨機(jī)分入實(shí)驗(yàn)組和對照組,各組年齡、性別相當(dāng),隨機(jī)時(shí)可按以下方式分層:移植前的ChildPugh A/B/C分級。其中實(shí)驗(yàn)組在肝移植術(shù)中及術(shù)后第3天給予huc-MSC靜脈輸注,劑量為1×106/kg(制備成50ml的細(xì)胞懸液),同時(shí)采用標(biāo)準(zhǔn)的免疫抑制方案。對照組為采用標(biāo)準(zhǔn)免疫抑制方案的肝臟移植患者。計(jì)劃每位患者都將接受12個(gè)月以上的隨訪。評估時(shí)間點(diǎn):術(shù)前;術(shù)后第3天;術(shù)后第7天;術(shù)后第1個(gè)月;術(shù)后第2個(gè)月;術(shù)后第3個(gè)月;術(shù)后第6個(gè)月;術(shù)后第12個(gè)月;各時(shí)間點(diǎn)評估項(xiàng)目有血生化;免疫功能指標(biāo);急、慢性排斥反應(yīng)發(fā)生率;感染發(fā)生率;移植相關(guān)并發(fā)癥發(fā)生率(肝動脈并發(fā)癥、門靜脈并發(fā)癥、膽道并發(fā)癥)。一旦出現(xiàn)急、慢性排斥反應(yīng),患者無須等待訪視時(shí)間節(jié)點(diǎn),須立即到醫(yī)院就診,并退出本次研究。本實(shí)驗(yàn)采用SPSS 19.0統(tǒng)計(jì)軟件完成。計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差((?)±s)表示,兩組連續(xù)變量的比較應(yīng)用Wilcoxon秩和檢驗(yàn),計(jì)數(shù)資料用X~2檢驗(yàn)或Fisher精確檢驗(yàn),P0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:與對照組相比,術(shù)后第3、7天實(shí)驗(yàn)組在外周血的CD4+CD25+(調(diào)節(jié)性T細(xì)胞)含量高于對照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),CD4+(輔助性/誘導(dǎo)性T細(xì)胞)含量及CD4+/CD8+T淋巴細(xì)胞的比值低于對照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),術(shù)后谷丙轉(zhuǎn)氨酶、總膽紅素的差異無統(tǒng)計(jì)學(xué)意義(P0.05),實(shí)驗(yàn)組術(shù)后肝功能異常事件的發(fā)生率明顯低于對照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),兩組移植后相關(guān)并發(fā)癥的發(fā)生率、感染發(fā)生率的差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:肝移植術(shù)后靜脈輸注huc-MSC安全可行;早期可促進(jìn)CD4+CD25+(調(diào)節(jié)性T細(xì)胞)的增殖和活化,降低CD4+輔助性/誘導(dǎo)性T細(xì)胞)含量及CD4+/CD8+T淋巴細(xì)胞的比值進(jìn)而改善肝移植受者免疫狀態(tài)。
[Abstract]:Objective: Long-term immunosuppression can significantly increase the probability of malignant tumors and infectious diseases in transplant recipients. Immunosuppressive agents can not prevent or delay the occurrence of chronic graft rejection. In recent years, it has been reported that MSCs have the ability of immune regulation, which can induce stable immune tolerance, and thus help to reduce the incidence of transplantation immune rejection. The aim of this study was to compare the immune indexes, the incidence of adverse events, the incidence of associated complications, and the liver function after liver transplantation in patients treated with huc-MSC and those who received only routine immunosuppressive therapy. To evaluate the safety and feasibility of clinical application of huc-MSC. Methods: from July 2014 to November 2015, a total of 40 patients with liver allograft were randomly divided into the experimental group and the control group according to the time of the operation. The age and sex of each group were the same as those of the control group, and 40 patients received liver allotransplantation at the liver transplantation center of the PLA 81 Hospital from July 2014 to November 2015. At random, it can be stratified as follows: Child-Pugh A / B / C grade prior to transplantation. In the experimental group, huc-MSC was given intravenously during and 3 days after liver transplantation at a dose of 1 脳 106% kg-1 脳 10 ~ (-6) 路kg ~ (-1) 50ml, and the standard immunosuppressive protocol was used. The control group was treated with standard immunosuppressive regimen for liver transplantation. Each patient is scheduled to be followed up for more than 12 months. Evaluation time points: preoperative; postoperative 3 d; postoperative 7 d; postoperative 1 month; postoperative 2 months; postoperative 3 months; postoperative 6 months; postoperative 12 months; Incidence of acute and chronic rejection; incidence of infection; incidence of transplant related complications (hepatic artery complication, portal vein complication, biliary tract complication). Once acute, chronic rejection occurs, the patient does not have to wait for the visit time node, must immediately visit the hospital, and withdraw from the study. The experiment was completed by SPSS 19.0 software. The two groups of continuous variables were compared by Wilcoxon rank sum test. The count data were calculated by X2 test or Fisher accurate test (P0.05). The difference was statistically significant. Results: compared with the control group, the CD4 CD25 (regulatory T cell) content in peripheral blood of the experimental group was higher than that of the control group on the 3rd day after operation. The difference was statistically significant (P 0.05) in CD4 (helper / inducible T cell) and the ratio of CD4 / CD8 T lymphocytes in the control group. The difference was statistically significant (P 0.05). There was no significant difference in total bilirubin (P 0.05). The incidence of abnormal hepatic function in the experimental group was significantly lower than that in the control group (P 0.05). There was no significant difference in the incidence of postoperative complications and infection between the two groups. Conclusion: intravenous infusion of huc-MSC after liver transplantation is safe and feasible, and can promote the proliferation and activation of CD4 CD25 (regulatory T cells) in the early stage. The ratio of CD4 / CD8 T lymphocytes and the ratio of CD4 / CD8 T lymphocytes were decreased to improve the immune status of the recipients of liver transplantation.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R657.3

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