中文摘要
肺动脉管道是心脏外科必需材料之一,但目前无理想的产品,组织工程学的发展为其研制提供了可能。我们已成功研制了低免疫原性的组织工程肺动脉管道,并得到国自然基金资助,但其低免疫原性的确切机制仍不清楚。在前期发现组织工程肺动脉管道凋亡与自噬相关基因与蛋白的分子表达有明显变化的基础上,本项目提出了“免疫-凋亡-自噬相互作用”假说,拟将低免疫原性的组织工程猪(供体)肺动脉片包埋在SD大鼠皮下,术后不同时间点收集样品进行免疫研究及转录组测序(RNA-Seq),利用KEGG pathway数据库来筛选免疫、凋亡、自噬差异基因;并用抗凋亡与自噬药物干扰后再进行免疫研究,进一步明确组织工程动脉的低免疫原性的凋亡、自噬基因通路。此项研究不仅能够证实免疫-凋亡-自噬相互作用假说的正确性科学性,而且以全新角度覆盖抗原来降低组织工程免疫原性打下坚实基础,此理念也将在移植免疫学、自身免疫疾病等领域有较广阔的应用前景。
英文摘要
Pulmonary arterial conduit is one of the requisites in cardiac surgery,but there has not been ideal product up to now. It is possible to be made true with development of tissue engineering. We sucessfully manufactured hypoimmuogenic tissue engineering pulmonarial arteries and got the support of National Natural Science Foundation of China. But their definite immununological mechanisms has not been made clear. The preliminary study shew that there were obvious changes in apoptosis and autophagy related gene and protein expression. So we raise up ‘immune-apoptosis-autophagy’ hypothesis. We will embed the tissue engineering arterial slices into SD rat subcutaeous. After the operation the samples will be collected in different times to carry out immunological research and Transcriptome Sequencing (RNA-Seq). KEGG pathway Database is used to screen the immune, apoptosis and autophagy related differential genes and after the interference with anti- apoptosis and anti-autophagy the immunological research will be done to definite the apoptosis and autophagy related gene paths. This item will prove the correctness of the hypothesis and lay a theoretical foundation for the tissue engineering to reduce immunogenicity with new point of view of covering antigens. There will be broader untilization prospects in transplantion immunology and autoimmune diseases.
