Chajara A, Raoudi M, Delpech B, Courel M, Leroy M, Basuyau J P, Levesque H
Laboratoire DIFEMA-MERCI, Faculté de Médecine-Pharmacie, CHU Rouen-Bois-Guillaume, Rouen, France.
J Vasc Res. 1999 May-Jun;36(3):209-21. doi: 10.1159/000025644.
The present study was conducted to determine the effect of diabetes with and without insulin treatment on the production of hyaluronen (HA) and distribution of hyaluronectin (HN) in the rat aorta 14 days after injury with a catheter balloon. Injury increased intima-media wet weight (+11%) and DNA content (+37.5%). This increase was slightly enhanced in untreated diabetic rats (+14.7% for wet weight and +48.9% for DNA content) and was significantly greater in diabetic rats treated with insulin (+28.9% for wet weight and +54% for DNA content). HA content increase in the injured aorta of nondiabetic rats (+43.6%) was similar in untreated diabetic (+44.7%) and more pronounced in diabetic rats treated with insulin (+91.3%). HA was markedly expressed in the neointima of nondiabetic rats, particularly near the lumen of the aorta. In untreated diabetic rats, HA was present throughout the neointima and not mainly close to the lumen. HA staining in the neointima of diabetic rats treated with insulin was similar to that in nondiabetic rats. HN was strongly expressed throughout the neointima of all groups. Injury enhanced the production of a high molecular mass HN (>400 kDa); this was not observed either in untreated or in insulin-treated diabetic rats. In conclusion, insulin treatment promoted the proliferative response of aorta to injury and this was associated mainly with increased HA production. This finding suggests that HA, which has been shown to play a crucial role in smooth muscle cell proliferation and migration, may be involved in the promoting effect of insulin treatment on arterial wall reaction to injury.
本研究旨在确定糖尿病及胰岛素治疗与否对大鼠主动脉球囊损伤14天后透明质酸(HA)产生及透明质连接蛋白(HN)分布的影响。损伤使内膜-中膜湿重增加(+11%),DNA含量增加(+37.5%)。在未治疗的糖尿病大鼠中,这种增加稍有增强(湿重增加+14.7%,DNA含量增加+48.9%),而在接受胰岛素治疗的糖尿病大鼠中增加更为显著(湿重增加+28.9%,DNA含量增加+54%)。非糖尿病大鼠损伤主动脉中HA含量增加(+43.6%),未治疗的糖尿病大鼠中类似(+44.7%),而在接受胰岛素治疗的糖尿病大鼠中更为明显(+91.3%)。HA在非糖尿病大鼠的新生内膜中显著表达,尤其靠近主动脉腔处。在未治疗的糖尿病大鼠中,HA存在于整个新生内膜,并非主要靠近管腔。接受胰岛素治疗的糖尿病大鼠新生内膜中的HA染色与非糖尿病大鼠相似。HN在所有组的整个新生内膜中均强烈表达。损伤增强了高分子量HN(>400 kDa)的产生;在未治疗或接受胰岛素治疗的糖尿病大鼠中均未观察到这种情况。总之,胰岛素治疗促进了主动脉对损伤的增殖反应,这主要与HA产生增加有关。这一发现表明,已被证明在平滑肌细胞增殖和迁移中起关键作用的HA,可能参与了胰岛素治疗对动脉壁损伤反应的促进作用。