异种超急性和急性血管排斥反应免疫病理研究
发布时间：2018-11-23 11:36
【摘要】：目的：研究慢病毒介导RNA干扰小鼠供心al,3GT、NF-κB表达后异种移植物的存活时间与免疫病理变化。 方法：采用改良Heron技术套袖法建立小鼠到大鼠异种异位心脏移植模型(小鼠心脏移植到大鼠右侧颈部)。按照RNA干扰供心靶基因不同分组：对照组、空病毒组、RNAiα1,3GT组、RNAi NF-κB组、RNAα1,3GT+NF-κB组,每组8对。观察移植供心存活时间,并使用SABC法检测失功心脏补体C3、IgM、IgG、NK细胞、巨噬细胞、ICAM-1表达情况。 结果：对照组、空病毒组、RNAiα1,3GT组、RNAiNF-κB组、RNAiα1,3GT+NF-κB组异种移植物的平均存活时间分别为(32±2.5)h,(31±2.5)h,(51±4.0)h,(31±1.8)h,(53±7.3)h.对照组、空病毒组、RNAiNF-κB组三组移植物生存时间无明显差别(p0.05),RNAial,3GT组、RNAial,3GT+NF-κB组移植物生存时间较对照组、空病毒组、RNAiNF-κB组明显延长(p0.05), RNAiα1,3GT组、RNAiα1,3GT+ NF-κB组两组移植物生存时间无明显差别(p0.05)。 SABC法检测补体C3、IgM、IgG在对照组、空病毒组、RNAi NF-κB组三组均可见大量沉积,且三组间无明显差别(p0.05)。RNAiα1,3GT组、RNAiα1,3GT+NF-κB组补体C3、IgM、IgG沉积较对照组、空病毒组、RNAiNF-KB组减少(p0.05), RNAiα1,3GT组、RNAiα1,3GT+NF-κB组两组间补体C3、IgM、IgG沉积无明显差别(p0.05)；NK细胞、巨噬细胞、ICAM-1在对照组、空病毒组、RNAiNF-KB组三组有阳性表达,且三组间无明显差别(p0.05),在RNAiα1，3GT组、RNAiα1,3GT+NF-κB组浸润表达较对照组、空病毒组、RNAiNF-κB组增加(p0.05),且RNAiα1,3GT+NF-κB组较RNAiα1,3GT组减少(p0.05)。 结论：异种抗原Galα(1,3)Gal在小鼠到大鼠异种心脏移植中起重要作用,RNAi可减少其表达使移植物存活时间延长,使异种移植物中补体C3、IgN、IgG沉积减少,巨噬细胞、自然杀伤细胞浸润增加,细胞间黏附分子-1表达增加,呈现为由HAR向AVR转变的趋势。小鼠到大鼠异种移植排斥具有HAR为主且与AVR共存的特点。RNAi NF-κB,可使移植物巨噬细胞、自然杀伤细胞浸润减少,细胞间黏附分子表达减低,可能减轻异种AVR反应。
[Abstract]:Aim: to study the survival time and immunopathologic changes of xenografts after lentivirus-mediated RNA interfering with the expression of al,3GT,NF- 魏 B in donor heart of mice. Methods: the model of heterotopic heart transplantation from mice to rats was established by modified Heron technique. According to RNA interference donor target gene, there were 8 pairs in each group: control group, empty virus group, RNAi 伪 1t3GT group, RNAi NF- 魏 B group, RNA 伪 1t3GT NF- 魏 B group. The survival time of donor heart was observed, and the expression of ICAM-1, macrophage and NK cells were detected by SABC method. Results: the mean survival time of xenografts in the control group, empty virus group, RNAi 伪 1t3GT group, RNAiNF- 魏 B group and RNAi 伪 1t3GT NF- 魏 B group was (32 卤2.5) h, (31 卤2.5) h, (51 卤4.0) h, (31 卤1.8) h, (53 卤7.3) h, respectively. The graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group, empty virus group and RNAiNF- 魏 B group (p0.05), and the graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group (p0.05), and the graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group (p0.05). There was no significant difference in graft survival time between RNAi 伪 1C 3GT group and RNAi 伪 1G 3GT NF- 魏 B group (p0.05). A large amount of SABC was found in the control group, empty virus group and RNAi NF- 魏 B group, and there was no significant difference among the three groups (p0.05). RNAi 伪 1t3GT, RNAi 伪 1t3GT NF- 魏 B group). In the empty virus group, there was no significant difference between the two groups (p0. 05), RNAi 伪 1 + 3GT, RNAi 伪 1 + 3GT NF- 魏 B) (p0. 05). The positive expression of NK cells, macrophages and ICAM-1 was found in the control group, empty virus group and RNAiNF-KB group, and there was no significant difference among the three groups (p0.05). The infiltrating expression of RNAi 伪 1 + 3GT NF- 魏 B group was higher than that of the control group, and the expression of RNAi 伪 1 + 3GT NF- 魏 B group was higher than that of the empty virus group. RNAiNF- 魏 B group increased (p0.05), and RNAi 伪 1t3GT NF- 魏 B group decreased compared with RNAi 伪 1t3GT group (p0.05). Conclusion: xenogeneic antigen Gal 伪 (1t3) Gal plays an important role in xenotransplantation from mice to rats. RNAi can decrease the expression of RNAi and prolong the survival time of graft, decrease the accumulation of complement C3IgNnnnnnnnhus in xenografts, and induce macrophages. The infiltration of natural killer cells increased and the expression of intercellular adhesion molecule-1 increased, which showed the trend of HAR to AVR. Xenograft rejection from mice to rats was characterized by HAR and co-existence with AVR. RNAi NF- 魏 B could reduce the infiltration of graft macrophages and natural killer cells, and decrease the expression of intercellular adhesion molecules, which might reduce the AVR response of xenogeneic cells.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392.3
本文编号：2351461
[Abstract]:Aim: to study the survival time and immunopathologic changes of xenografts after lentivirus-mediated RNA interfering with the expression of al,3GT,NF- 魏 B in donor heart of mice. Methods: the model of heterotopic heart transplantation from mice to rats was established by modified Heron technique. According to RNA interference donor target gene, there were 8 pairs in each group: control group, empty virus group, RNAi 伪 1t3GT group, RNAi NF- 魏 B group, RNA 伪 1t3GT NF- 魏 B group. The survival time of donor heart was observed, and the expression of ICAM-1, macrophage and NK cells were detected by SABC method. Results: the mean survival time of xenografts in the control group, empty virus group, RNAi 伪 1t3GT group, RNAiNF- 魏 B group and RNAi 伪 1t3GT NF- 魏 B group was (32 卤2.5) h, (31 卤2.5) h, (51 卤4.0) h, (31 卤1.8) h, (53 卤7.3) h, respectively. The graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group, empty virus group and RNAiNF- 魏 B group (p0.05), and the graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group (p0.05), and the graft survival time of RNAial,3GT group and RNAial,3GT NF- 魏 B group was significantly longer than that of control group (p0.05). There was no significant difference in graft survival time between RNAi 伪 1C 3GT group and RNAi 伪 1G 3GT NF- 魏 B group (p0.05). A large amount of SABC was found in the control group, empty virus group and RNAi NF- 魏 B group, and there was no significant difference among the three groups (p0.05). RNAi 伪 1t3GT, RNAi 伪 1t3GT NF- 魏 B group). In the empty virus group, there was no significant difference between the two groups (p0. 05), RNAi 伪 1 + 3GT, RNAi 伪 1 + 3GT NF- 魏 B) (p0. 05). The positive expression of NK cells, macrophages and ICAM-1 was found in the control group, empty virus group and RNAiNF-KB group, and there was no significant difference among the three groups (p0.05). The infiltrating expression of RNAi 伪 1 + 3GT NF- 魏 B group was higher than that of the control group, and the expression of RNAi 伪 1 + 3GT NF- 魏 B group was higher than that of the empty virus group. RNAiNF- 魏 B group increased (p0.05), and RNAi 伪 1t3GT NF- 魏 B group decreased compared with RNAi 伪 1t3GT group (p0.05). Conclusion: xenogeneic antigen Gal 伪 (1t3) Gal plays an important role in xenotransplantation from mice to rats. RNAi can decrease the expression of RNAi and prolong the survival time of graft, decrease the accumulation of complement C3IgNnnnnnnnhus in xenografts, and induce macrophages. The infiltration of natural killer cells increased and the expression of intercellular adhesion molecule-1 increased, which showed the trend of HAR to AVR. Xenograft rejection from mice to rats was characterized by HAR and co-existence with AVR. RNAi NF- 魏 B could reduce the infiltration of graft macrophages and natural killer cells, and decrease the expression of intercellular adhesion molecules, which might reduce the AVR response of xenogeneic cells.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392.3
【参考文献】
相关期刊论文 前5条
1 张明奎,胡建国,杨进福;ICAM-1在移植心脏缺血再灌注损伤中的表达及意义[J];中国医师杂志;2004年01期
2 戚峰,邱宇杰,王鹏志,朱理玮;小鼠-大鼠异种异位心脏移植模型的建立[J];天津医科大学学报;2001年02期
3 吴小蔚,陕声国,余墨生,程邦昌,王松山,李爱林;核因子κB抑制剂对缺血再灌注皮瓣TNF-α和ICAM-1表达的影响[J];中华显微外科杂志;2005年04期
4 陈刚,王西墨,郭晖,孙黔云,沈世乾,王虹,陈利君,吴瑛,王婉瑜,熊郁良,陈实;猪到猕猴异种心脏移植超急性排斥反应的免疫学及病理学变化[J];中华器官移植杂志;2005年01期
5 陈栋,曹荣华,郭晖,陈刚,王西墨,沈世乾,孙乾云,王虹,陈丽君,吴瑛,朱建国,王婉瑜,熊郁良,陈实;猪-猕猴延迟性异种移植排斥反应的发生机制[J];中国免疫学杂志;2005年01期
相关博士学位论文 前1条
1 周晓彤;利用siRNA抑制NF-κB p65蛋白的表达对Ⅱ型血管内皮细胞激活的影响的研究[D];苏州大学;2005年
，本文编号：2351461
本文链接：https://www.wllwen.com/yixuelunwen/shiyanyixue/2351461.html
最近更新
教材专著
