Dattilo J B, Dattilo M P, Crane J T, Yager D R, Makhoul R G
Hunter H. McGuire Veterans Administration Medical Center, Richmond, Virginia, USA.
J Surg Res. 1998 Jan;74(1):39-42. doi: 10.1006/jsre.1997.5224.
The success of vascular bypass procedures is limited by the development of intimal hyperplasia (IH). The nitric oxide (NO) precursor, L-arginine (L-ARG) significantly reduces IH in both arteries and experimental vein grafts; however, the precise mechanism has yet to be elucidated. Hyaluronan synthase-1 (HAS-1) is one of the two enzymes believed to be responsible for making hyaluronan, a key component extracellular matrix composition.
To determine how L-ARG supplementation affects the gene expression of HAS-1 in experimental vein grafts.
Thirty-four male New Zealand white rabbits were divided into three groups: control (no operation, regular chow and water, n = 4); L-ARG supplemented (n = 15); and no L-ARG (n = 15). The latter two groups underwent a right interposition carotid bypass using jugular vein. Vein grafts were harvested at 7, 14, and 21 days after surgery. Ribonuclease protection assays were performed using 32P-labeled riboprobes for HAS-1 and 18S rRNA as an internal control and expressed as a ratio (HAS-1/rRNA).
There was a significant rise in HAS-1 expression in the vein grafts 7 (1.57 +/- 0.5), 14 (0.7 +/- 0.2), and 21 days (2.82 +/- 0.7) after grafting compared to control (0.14 +/- 0.08) (P < 0.05). L-ARG-supplemented animals had a significant decrease in HAS-1 expression at 21 days (0.65 +/- 0.1) compared to nonsupplemented vein grafts (2.82 +/- 0.7) (P < 0.02).
These results demonstrate for the first time a significant rise in HAS expression in the early experimental vein grafts. Furthermore, L-ARG supplementation significantly diminishes the expression of HAS at 21 days. These results may represent a potential mechanism by which augmentation of the L-ARG/NO pathway inhibits IH in experimental vein grafts and may ultimately provide for improved therapeutic interventions in alleviating IH.
血管搭桥手术的成功受到内膜增生（IH）发展的限制。一氧化氮（NO）前体L-精氨酸（L-ARG）可显著减少动脉和实验性静脉移植物中的内膜增生；然而，确切机制尚待阐明。透明质酸合酶-1（HAS-1）是被认为负责合成透明质酸的两种酶之一，透明质酸是细胞外基质组成的关键成分。
确定补充L-ARG如何影响实验性静脉移植物中HAS-1的基因表达。
34只雄性新西兰白兔分为三组：对照组（未手术，给予常规饲料和水，n = 4）；补充L-ARG组（n = 15）；未补充L-ARG组（n = 15）。后两组采用颈静脉进行右颈间置旁路手术。术后7、14和21天采集静脉移植物。使用针对HAS-1的32P标记核糖探针和18S rRNA作为内对照进行核糖核酸酶保护分析，并以比值（HAS-1/rRNA）表示。
与对照组（0.14±0.08）相比，移植后7天（1.57±0.5）、14天（0.7±0.2）和21天（2.82±0.7）静脉移植物中HAS-1表达显著升高（P < 0.05）。与未补充L-ARG的静脉移植物（2.82±0.7）相比，补充L-ARG的动物在21天时HAS-1表达显著降低（0.65±0.1）（P < 0.02）。
这些结果首次证明在早期实验性静脉移植物中HAS表达显著升高。此外，补充L-ARG在21天时显著降低HAS的表达。这些结果可能代表了一种潜在机制，通过该机制增强L-ARG/NO途径可抑制实验性静脉移植物中的内膜增生，并最终可能为减轻内膜增生提供更好的治疗干预措施。
