Hoch J R, Stark V K, Hullett D A, Turnipseed W D
Department of Surgery, University of Wisconsin-Madison.
Surgery. 1994 Aug;116(2):463-70; discussion 470-1.
Intimal hyperplasia (IH), a cause of early graft failure, may be regulated by leukocyte-elaborated cytokines. We investigated leukocyte infiltration and cytokine gene expression in vein grafts.
Epigastric vein to femoral artery grafts were performed in Lewis rats and harvested on day 4 and weeks 1, 2, 4, 8, and 12. Neointimal areas were measured by computerized planimetry. Immunoperoxidase staining identified for macrophages, CD4+, CD8+, and major histocompatibility complex class II+ cells. Graft RNA was used in reversetranscription-polymerase chain reaction with interleukin (IL)-1 alpha, IL-2R, monocyte chemoattractant protein-1, and transforming growth factor-beta primers.
IH was measurable at 2 weeks; the perianastomotic regions displayed greater IH than the midgraft (p < 0.05). MANOVA indicated strong location (p = 0.0001) and time (p = 0.0009) effects. Immunocytochemistry showed inflammatory infiltrates from 4 days to 4 major histocompatibility complex class II+ and primarily monocyte/macrophages, with less frequent T lymphocytes (CD4+ > CD8+). IL-1 alpha messenger RNA is expressed early, disappearing after 4 weeks. Monocyte chemoattracta t protein-1 mRNA is constitutively expressed, with up-regulation at 4 days to 4 weeks. IL-2R mRNA levels fluctuate; transforming growth factor-beta is always expressed, peaking at 4 days to 4 weeks.
Gene expression of cytokines thought to modulate IH is up-regulated early in vein grafts. This coincides with graft infiltration by activated leukocytes before and during the development of IH.
内膜增生（IH）是早期移植物失败的一个原因，可能受白细胞分泌的细胞因子调节。我们研究了静脉移植物中的白细胞浸润和细胞因子基因表达。
在Lewis大鼠中进行腹壁静脉至股动脉移植，并于第4天以及第1、2、4、8和12周取材。通过计算机图像分析测量新生内膜面积。免疫过氧化物酶染色鉴定巨噬细胞、CD4⁺、CD8⁺和主要组织相容性复合体II类⁺细胞。将移植物RNA用于白细胞介素（IL）-1α、IL-2R、单核细胞趋化蛋白-1和转化生长因子-β引物的逆转录-聚合酶链反应。
2周时可检测到内膜增生；吻合口周围区域的内膜增生比移植物中部更明显（p<0.05）。多变量方差分析表明位置（p = 0.0001）和时间（p = 0.0009）有显著影响。免疫细胞化学显示，从第4天到第4周有炎症浸润，主要是主要组织相容性复合体II类⁺细胞和单核细胞/巨噬细胞，T淋巴细胞较少见（CD4⁺>CD8⁺）。IL-1α信使核糖核酸早期表达，4周后消失。单核细胞趋化蛋白-1信使核糖核酸持续表达，在第4天到第4周上调。IL-2R信使核糖核酸水平波动；转化生长因子-β始终表达，在第4天到第4周达到峰值。
被认为调节内膜增生的细胞因子的基因表达在静脉移植物早期上调。这与内膜增生发生之前及期间活化白细胞对移植物的浸润相一致。
