不同来源致耐受树突状细胞诱导大鼠同种异体牙移植免疫低反应的动态研究

发布时间：2018-02-11 12:35

本文关键词： 树突状细胞牙移植免疫耐受免疫排斥　出处：《重庆医科大学》2011年硕士论文　论文类型：学位论文

【摘要】：同种异体牙移植是修复缺失牙、恢复咀嚼功能的有效方法之一,但移植后出现的免疫排斥反应和牙根吸收是阻碍异体牙移植成功的关键。利用树突状细胞(dendritic cell,DC)作为细胞治疗,减轻免疫排斥反应或促进免疫耐受,是近年来受到关注的移植耐受诱导的新方法。目的: 本研究旨在通过利用致耐受DC诱导同种异体牙移植后形成免疫低反应或耐受,使移植牙能够长期存留并发挥功能,为临床研究和应用提供借鉴,奠定基础。方法: 培养供、受体来源的致耐受DC分别为BN大鼠(SPF级、6~8 w、120-160g、雄性)和Lewis大鼠(SPF级、6~8 w、150-200g、雄性)。建立牙移植模型供、受体大鼠分别为BN大鼠(清洁级、10-12w、180-230g、雄性)和Lewis大鼠(清洁级、10-12 w、260-320g、雄性)。将动物随机分为4组:A组为同基因型移植组, Lewis→Lewis; B、C、D组为同种异体牙移植组, BN→Lewis;A、B组于术前7d通过尾静脉输注PBS0.5ml于受体大鼠体内,C组于术前7d通过尾静脉输注1*106个/只的供体致耐受DC于受体大鼠体内,D组于术前7d通过尾静脉输注1*106个/只的受体致耐受DC于受体大鼠体内。各组于术后第1,2,4,8周随机处死5只大鼠,对移植牙进行病理学检测和ELISA检测外周血清IL-2、IFN-r、IL-4、IL-10浓度。结果: 1.血清细胞因子变化情况提示:C、D组IL-2、IFN-γ在各时间点均高于A组低于B组,IL-4、IL-10在各时间点均高于A、B组。C组IL-2在第1周时低于D组,到第8周时则高于D组。C组IL-4、IL-10在第1、2周时高于D组,到第8周时则低于D组。 2.炎性细胞浸润、牙根吸收及愈合情况提示:C、D组炎性细胞浸润较B组均明显减轻但重于A组。C、D组牙根吸收较B组有所减少但仍高于A组,C、D组牙根吸收点数在2、4周时没有差异,在8周时D组牙根吸收点数于少C组。C、D组牙周膜愈合点数多于B组但少于A组。B组炎性吸收点数多于A、C、D组。A组替代性吸收点数少于B、C、D。结论: 1.输注供、受体来源的致耐受DC,均可抑制Th1类细胞因子,诱导T淋巴细胞向Th2细胞偏倚,诱导Th2型细胞反应,显著地升高Th2/Th1比值,明显抑制了大鼠同种异体移植牙的排斥反应,减轻排斥反应程度。 2.输注供、受体来源的致耐受DC,均可以减少同种异体牙移植后炎性细胞浸润,可以减少同种异体牙移植后牙根的吸收,促进牙周膜的愈合。 3.供体来源的致耐受DC对早期急性排斥反应抑制更显著,受体来源的致耐受DC则对晚期慢性排斥反应抑制更显著。受体来源致耐受DC更能减少远期牙根的吸收。
[Abstract]:Allogeneic tooth transplantation is one of the effective methods to repair missing teeth and restore masticatory function. However, the immune rejection and root resorption after transplantation are the key to the success of dental allograft. Dendritic cell DCA is used as cell therapy. Reducing immune rejection or promoting immune tolerance is a new method to induce transplantation tolerance. Objective:. The purpose of this study was to induce low immune response or tolerance after allogeneic tooth transplantation by means of tolerance DC, so that the transplanted teeth could survive and function for a long time, and provide a reference for clinical research and application, and lay a foundation for clinical research and application. Methods:. The tolerant DC derived from the receptor were 120 ~ 160g (male) from 6w ~ 160g of SPF class in BN rats and 150-200g from 6wh ~ 200g of Lewis rat. The model of tooth transplantation was established. The recipient rats were BN rats (clean grade 10-12 weeks, 180-230 g, male) and Lewis rats (clean grade 10-12 wk, 260-320g, male). 鈫扡ewis; Bu Con D group is allograft group, BN group. 鈫扵he recipient rats in group C received PBS0.5ml 7 days before operation by intravenous infusion of PBS0.5ml through caudal vein to induce tolerance of DC to recipient rats by infusion of 1 * 106 DC per donor on the 7th day before operation. In group D, 1 * 106 rats were injected through caudal vein on 7 days before operation. Receptor-induced DC tolerance was found in the recipient rats. Five rats were randomly killed in each group at 8 weeks after operation. The levels of IL-4 and IL-10 in peripheral blood were detected by pathological examination and ELISA. Results:. 1. The changes of serum cytokines showed that the level of IL-2IFN- 纬 in group C was higher than that in group A and group B at each time point, and the level of IL-4IL-10 in group C was higher than that in group D at the first week, and that in group C was higher than that in group D at week 1. At the 8th week, IL-4IL-10 in group C was higher than that in group D at week 1. At week 8, it was lower than group D. 2. The infiltration of inflammatory cells, root resorption and healing showed that the infiltration of inflammatory cells in group D was significantly less than that in group B, but more serious than that in group A. The number of root resorption in group C was lower than that in group B, but still higher than that in group A, and there was no difference in the number of resorption points between group C and group C at 2 weeks. At 8 weeks, the number of root resorption in group D was more than that in group B, but less than that in group A, group B, and the number of alternative resorption points in group A was less than that in group A. Group A was less than that in group B. Conclusion:. 1. Th1 cytokines were inhibited, T lymphocytes were biased toward Th2 cells, Th2 type cells were induced to react, the ratio of Th2/Th1 was significantly increased, and the rejection of allograft teeth was significantly inhibited. Reduce the degree of rejection. 2.Infusion and donor, receptor-induced tolerance DC2 can reduce the infiltration of inflammatory cells, decrease the root resorption and promote the healing of periodontal ligament after allogeneic tooth transplantation. 3.The donor-derived DC inhibited the early acute rejection more significantly, while the receptor-derived DC inhibited the late chronic rejection more significantly, and the receptor-derived tolerant DC decreased the long-term root resorption more significantly.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392

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