Schiller N K, Timothy A M, Chen I L, Rice J C, Akers D L, Kadowitz P J, McNamara D B
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol. 1999 Aug;277(2):H740-8. doi: 10.1152/ajpheart.1999.277.2.H740.
Neointimal thickening after catheter injury has been reported to be influenced by the integrity of the vascular endothelium. We have previously shown that neointimal thickening is significantly reduced in alloxan-induced diabetic New Zealand White rabbits after catheter injury compared with euglycemic rabbits. In the present study, it was hypothesized that endothelial cell regrowth, morphology, and endothelium-dependent vasoreactivity after catheter injury are improved in the diabetic rabbit (glucose >/=400 mg/dl) compared with the euglycemic rabbit. Two weeks after catheter injury, the percent endothelial regrowth was significantly increased in diabetic animals compared with euglycemic animals (32.1 +/- 2 and 15.6 +/- 1, respectively; P < 0.05). The endothelial cell morphology analyzed by scanning electron microscopy was also restored 2 wk after catheter injury in thoracic aortas from the diabetic animals compared with vessels from euglycemic animals. Endothelium-dependent relaxation to ACh in vessels from diabetic and euglycemic rabbits was attenuated 2 wk after injury, and, although improved by 4 and 8 wk, relaxation remained significantly depressed. These results suggest that endothelial cell regrowth and morphology in diabetic animals was improved compared with euglycemic animals; however, endothelium-dependent vasoreactivity remained impaired. Thus the attenuated neointimal thickening seen in the diabetic rabbit may be a function of the rate and degree of regrowth rather than the normalization of ACh-induced relaxation.
据报道，导管损伤后的新生内膜增厚受血管内皮完整性的影响。我们之前已经表明，与血糖正常的家兔相比，用四氧嘧啶诱导的糖尿病新西兰白兔在导管损伤后新生内膜增厚明显减轻。在本研究中，我们假设与血糖正常的家兔相比，糖尿病家兔（血糖≥400mg/dl）在导管损伤后的内皮细胞再生、形态以及内皮依赖性血管反应性会得到改善。导管损伤两周后，与血糖正常的动物相比，糖尿病动物的内皮再生百分比显著增加（分别为32.1±2和15.6±1；P<0.05）。与血糖正常动物的血管相比，糖尿病动物胸主动脉在导管损伤2周后通过扫描电子显微镜分析的内皮细胞形态也得到恢复。损伤2周后，糖尿病和血糖正常家兔血管对乙酰胆碱的内皮依赖性舒张减弱，虽然在4周和8周时有所改善，但舒张仍显著受到抑制。这些结果表明，与血糖正常的动物相比，糖尿病动物的内皮细胞再生和形态得到改善；然而，内皮依赖性血管反应性仍然受损。因此，糖尿病家兔中观察到的新生内膜增厚减轻可能是再生速率和程度的作用，而非乙酰胆碱诱导舒张恢复正常的结果。
