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通过大鼠腹主动脉移植模型研究乙二胺四乙酸-聚乙烯亚胺肝素化对同种异体血管抗原及炎症水平的影响。

Effects of EDC-PEI heparinization on allogeneic vascular antigens and inflammation levels via a rat abdominal aorta transplantation model.

作者信息

Han Feng, Tian Puxun, Xia Xinxin, Wang Yuxiang, Dou Meng, Zheng Jin, Ding Xiaoming, Xue Wujun, Ding Chenguang

机构信息

Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Exp Ther Med. 2018 Dec;16(6):5053-5058. doi: 10.3892/etm.2018.6879. Epub 2018 Oct 19.

Abstract

The objective of this study was to investigate the possibility of increasing the remote patency rate of allogeneic vessel transplantation through studying the effects of N-ethyl-N-(3-dimethylaminopropyl)-carbodiimide and polyethyleneimine (EDC-PEI) heparinization on allogeneic vascular antigens and inflammation levels. Forty rats were randomly divided into the control group, the EDC group, the PEI group and the EDC-PEI group. The rat abdominal aorta was used as the object of study, and the transplanted blood vessels were pretreated with EDC as the water-soluble cross-linking agent and PEI as the heparin-coated carrier. A rat abdominal aorta allogeneic transplantation model was established. Ultrasonic examination was used for observation of patency of proximal and distal anastomosis in each group. The tissue repair after abdominal aorta transplantation in each group was examined by H&E staining. The biomechanics, denaturation temperature and blasting strength of each group were compared. The levels of IL-1, IL-6 and TNF-α in serum of rats were measured by ELISA method, and the expression of MHC-II and α-GAL antigens in blood vessels were detected by immunohistochemistry. There were different degrees of thickening and inflammatory cell aggregation in the abdominal aorta of rats in the control, EDC and PEI groups, but there was no obvious lesion in the EDC-PEI group. Compared with the four groups, the mechanical characteristics of the EDC group decreased significantly, and the stenosis rate of anastomotic stoma in the EDC group was higher than that in the EDC-PEI and PEI groups (P<0.05). The denaturation temperature of the PEI group was lower than that of the EDC and EDC-PEI groups (P<0.05). The mechanical property and vascular bursting strength in the EDC-PEI group were similar to those in the control group. At the same time, it has more significant advantages than the other three groups in removing the vascular antigens MHC-II and α-GAL and reducing the level of inflammatory reaction, thus increasing the remote patency rate of allogeneic vascular transplantation. The inflammatory response and vascular antigenicity after transplantation are effectively reduced via the rat abdominal aorta transplantation model treated with allogeneic EDC-PEI heparinization, which has a higher remote patency rate.

摘要

本研究的目的是通过研究N-乙基-N-(3-二甲氨基丙基)-碳二亚胺和聚乙烯亚胺(EDC-PEI)肝素化对同种异体血管抗原和炎症水平的影响,探讨提高同种异体血管移植远期通畅率的可能性。将40只大鼠随机分为对照组、EDC组、PEI组和EDC-PEI组。以大鼠腹主动脉为研究对象,采用水溶性交联剂EDC和肝素包被载体PEI对移植血管进行预处理。建立大鼠腹主动脉同种异体移植模型。采用超声检查观察各组近、远端吻合口的通畅情况。通过苏木精-伊红染色检查各组腹主动脉移植后的组织修复情况。比较各组的生物力学、变性温度和爆破强度。采用酶联免疫吸附测定法检测大鼠血清中白细胞介素-1、白细胞介素-6和肿瘤坏死因子-α的水平,采用免疫组织化学法检测血管中主要组织相容性复合体-II(MHC-II)和α-半乳糖抗原的表达。对照组、EDC组和PEI组大鼠腹主动脉均有不同程度的增厚和炎性细胞聚集,而EDC-PEI组未见明显病变。与四组相比,EDC组的力学特性显著降低,EDC组吻合口狭窄率高于EDC-PEI组和PEI组(P<0.05)。PEI组的变性温度低于EDC组和EDC-PEI组(P<0.05)。EDC-PEI组的力学性能和血管爆破强度与对照组相似。同时,其在去除血管抗原MHC-II和α-半乳糖以及降低炎症反应水平方面比其他三组具有更显著的优势,从而提高了同种异体血管移植的远期通畅率。通过对同种异体EDC-PEI肝素化处理的大鼠腹主动脉移植模型,有效降低了移植后的炎症反应和血管抗原性,其远期通畅率更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a1b/6257806/fb891e70e2ac/etm-16-06-5053-g00.jpg

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