乙酰肝素酶诱导大鼠移植动脉硬化的作用

Heparanase induces transplant arteriosclerosis of abdominal aortic allografts

目的 探讨乙酰肝素酶在同种异体血管移植中的作用及其与移植动脉硬化的关系。方法 实验分为两组，实验组：以Wistar大鼠为供者，SD大鼠为受者，取供者肾下腹主动脉（长约1cm），正位替换受者同部位主动脉，建立腹主动脉移植模型。对照组：仅将SD大鼠相应的腹主动脉切断后再行原位吻合。术后60d时，应用逆转录聚合酶链反应、免疫组织化学法和计算机图像分析方法分别检测各组腹主动脉的乙酰肝素酶水平、炎性细胞浸润程度（ED1、CD4细胞）、腹主动脉内膜厚度及管腔面积。结果 实验组移植的腹主动脉中乙酰肝素酶表达较对照组明显增加；实验组ED1及CD4细胞阳性表达率分别为（44．8±12．5）％和（37．6±7．9）％，对照组分别为（8．9±3．7）％和（10．3±5．6）％，两组相比，差异有统计学意义（P〈0．01）。实验组移植腹主动脉内膜厚度增加，管腔面积减少，与对照组比较，差异有统计学意义（P〈0．05）。结论 免疫炎性细胞可通过激活乙酰肝素酶介导移植的腹主动脉损伤，促进动脉硬化形成。

Objective To explore role of heparanase in vascular response to abdominal aortic allografts and its relation to transplant arteriosclerosis. Methods A segment of infra-renal abdominal aorta was transplanted orthotopically from Wistar to SD rats, and the same aorta of SD rats was divided and re-anastomosed as the controls. Aortic grafts were analyzed separately on day 60 after transplantation by reverse-transcriptase polymerase chain reaction （RT-PCR）, immunohistochemistry and morphometry for the detection of heparanase mRNA production, infiltration of ED1 inflammatory macrophages and CD4 T lymphocytes, and intimal thickness and luminal areas by a computer-assisted technique. Results In contrast to the controls, the expression of heparanase, ED1, CD4 and intimal thickness were increased obviously, while luminal areas decreased accordingly and significantly in experimental groups. Conclusion Immune inflammation damage to abdominal aorta after allograft, mediated by activated heparanase,can induce transplant arteriosclerosis.