發(fā)布時間：2018-07-10 02:16

  本文選題：轉(zhuǎn)化生長因子-β1 + 骨髓間充質(zhì)干細(xì)胞　； 參考：《昆明醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的通過注射外源性轉(zhuǎn)化生長因子β1(TGF-β1)轉(zhuǎn)染骨髓間充質(zhì)干細(xì)胞(MSC)予兔胰腺移植(PTA)模型受體,探討TGF-β1修飾MSC能否誘導(dǎo)移植胰腺免疫耐受。材料和方法1.采用健康幼齡日本大耳白兔24只,隨機(jī)抽出12只作單獨(dú)胰腺移植(PTA)的供體,余12只制作糖尿病模型,模型成功后成為PTA的受體。將受體分成(A、B、C、D)組,給予不同處理,A組：受體胰腺移植前5天給予MSC靜脈輸注,B組：受體胰腺移植前5天給予TGF-β1轉(zhuǎn)染MSC靜脈輸注,C組：受體胰腺移植前5天只給TGF-β1,D組：空白組,受體胰移植前不行干預(yù)。2.對供體進(jìn)行分離、灌注、切取、修剪供體胰腺；分離受體一側(cè)腎后,阻斷腎動靜脈,用袖套法完成供體門靜脈與受體腎靜脈的吻合,用縫合法完成腹腔干動脈與腎動脈吻合,輸尿管和胰管置管行膀胱內(nèi)引流。3.對術(shù)后受體進(jìn)行處理,取各組移植兔術(shù)后不同時間的靜脈血及尿液來測定內(nèi)外分泌功能,并對術(shù)后死亡兔子進(jìn)行病理檢查分析。4.對術(shù)后受體進(jìn)行處理,取各組移植兔術(shù)后第1、3天共2個時間段靜脈血,應(yīng)用流式細(xì)胞儀檢測CD4+T細(xì)胞和CD8+T細(xì)胞百分率,并計(jì)算其比值及CD4+CD25+Treg細(xì)胞的比例。結(jié)果1. 12只供體順利完成胰腺切取術(shù),12只受體成功制作糖尿病模型并順利完成胰腺移植術(shù)；供體胰腺移植后迅速恢復(fù)血液循環(huán),無出血及漏血；術(shù)后1例死于靜脈血栓形成,實(shí)驗(yàn)組的9只受體術(shù)后平均生存期(8.0±0.7)d,對照組的3只受體術(shù)后平均生存期(7.0±0.2)d,成功建立兔胰腺移植模型。2.術(shù)后實(shí)驗(yàn)組胰腺內(nèi)外分泌功能在存活期間比對照組好,差異有統(tǒng)計(jì)學(xué)意義(P0.05),病理檢查結(jié)果顯示明顯比對照組排斥反應(yīng)低。3.術(shù)后MSC組(n=3)比未干預(yù)組(n=3) CD4+T細(xì)胞數(shù)和CD4+CD25+Treg細(xì)胞數(shù)比例高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。4.術(shù)后TGF-β1轉(zhuǎn)染MSC組(n=3)比未干預(yù)組(n=3) CD4+T細(xì)胞數(shù)和CD4+CD25+Treg細(xì)胞數(shù)比例低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。5.術(shù)后TGF-β1組(n=3)比未干預(yù)組(n=3) CD4+T細(xì)胞數(shù)和CD4+CD25+Treg細(xì)胞數(shù)比例高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。6.術(shù)后TGF-β1轉(zhuǎn)染MSC組(n=3)比MSC組(n=3)、TGF-β1組(n=3) CD4+T細(xì)胞數(shù)和CD4+CD25+Treg細(xì)胞數(shù)比例高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論TGF-β1轉(zhuǎn)染MSC能夠調(diào)節(jié)動物胰腺移植免疫反應(yīng),可減輕排斥反應(yīng),較單獨(dú)使用MSC或TGF-β1免疫效果明顯。
[Abstract]:Objective to investigate whether TGF- 尾 1 modified mesenchymal stem cells (MSC) can induce pancreatic allograft tolerance by injecting exogenous transforming growth factor 尾 1 (TGF- 尾 1) into rabbit pancreatic transplantation (PTA) model receptor. Materials and methods 1. A total of 24 healthy young Japanese large ear white rabbits were randomly selected as donors for pancreas transplantation (PTA) and 12 diabetic models were established. The recipients were divided into two groups: group A: group B received MSC intravenous infusion 5 days before pancreas transplantation: group C received TGF- 尾 1 transfection into MSC 5 days prior to pancreatic transplantation: group D: group B: TGF- 尾 1C: group D: group B: TGF- 尾 1D: group C: TGF- 尾 1D: group D: group B: TGF- 尾 1D: group C: TGF- 尾 1D; The receptor did not intervene before pancreas transplantation. The donor was separated, perfused, cut off and pruned the donor pancreas, after separating the recipient kidney, the renal artery and vein were blocked, the donor portal vein and the recipient renal vein were anastomosed with cuff method, and the abdominal trunk artery and renal artery were anastomosed by suture. Ureteral and pancreatic duct catheters were placed for intravesical drainage. The recipient was treated and the venous blood and urine were taken from each group of rabbits at different time after transplantation to determine the function of exocrine and exocrine secretion, and the pathological examination and analysis of the dead rabbits after operation were made. 4. The recipients were treated and the venous blood was taken from the rabbits at the 1st day after transplantation. The percentages of CD4 T cells and CD8 T cells were measured by flow cytometry, and the ratio of CD4 CD25 Treg cells were calculated. Result 1. 12 donors successfully completed pancreatic excision and 12 recipients successfully made diabetic models and successfully completed pancreas transplantation; donor pancreas transplantation quickly recovered blood circulation without bleeding or bleeding; 1 case died of venous thrombosis after operation. The mean survival time of 9 recipients was (8.0 鹵0.7) days in the experimental group and (7.0 鹵0.2) days in the control group. The exocrine and exocrine pancreatic function in the experimental group was better than that in the control group during the survival period, the difference was statistically significant (P0.05). The pathological results showed that the rejection was significantly lower than that in the control group. The percentage of CD4 T cells and CD4 CD25 Treg cells in MSC group was higher than that in non-intervention group (P0.05). The percentage of CD4 T cells and CD4 CD25 Treg cells in MSC transfected with TGF- 尾 1 was significantly lower than that in control group (P0.05). The ratio of CD4 T cells and CD4 CD25 Treg cells in TGF- 尾 1 group was higher than that in non-intervention group (P0.05). The percentage of CD4 T cells and CD4 CD25 Treg cells in TGF- 尾 1 transfected MSC group was higher than that in MSC group after operation (P0.05). Conclusion transfection of MSC with TGF- 尾 1 can modulate the immune response of pancreas transplantation and alleviate rejection, which is more effective than that of MSC or TGF- 尾 1 alone.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R657.5

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本文編號：2111630