高同型半胱氨酸血症对球囊损伤大鼠颈动脉新生内膜增生的影响

Neointimal hyperplasia in balloon-injured rat carotid arteries: the influence of hyperhomocysteinemia.

作者信息

Cook Judith W, Malinow M Rene, Moneta Gregory L, Taylor Lloyd M, Orloff Susan L

机构信息

Division of Liver/Pancreas Transplantation, Hepatobiliary Surgery, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA.

出版信息

J Vasc Surg. 2002 Jan;35(1):158-65.

PMID:11802148

Abstract

PURPOSE

Hyperhomocyst(e)inemia (hH[e]) is a risk factor for atherosclerosis. Neointimal hyperplasia (NH) after vessel injury can contribute to atherosclerosis. In this study, we investigated the effects of hH(e) on NH formation after arterial balloon injury in rats.

METHODS

Lewis rats that were given a hH(e)-inducing (high methionine, low folate) or normal diet for 150 days underwent common carotid artery (CCA) balloon injury. Two and 4 weeks after injury, CCAs were formalin perfusion-fixed, sectioned, and stained for elastin. Neointimal index (NI, percent lumen occlusion) and neointima (N) and media (M) area were measured by using computer-interfaced microscopy.

RESULTS

Plasma homocyst(e)ine (H[e]) levels were elevated in rats given the study diet compared with rats given the normal diet at days 40 and 90 (69 +/- 8 and 73 +/- 9 micromol/L vs 4 +/- 0.4 and 4 +/- 0.6 micromol/L, P <.001). After balloon injury, the CCA NI and N/M ratio, but not the M area, were increased by hH(e) compared with normal plasma H(e) (2 weeks [n = 6,7]: NI = 7.3 +/- 1.7 vs 2.9 +/- 0.7, P =.002, and N/M = 0.31 +/- 0.08 vs 0.08 +/- 0.02, P <.001; 4 weeks [n = 4,7]: NI = 13.1 +/- 2.2 vs 6.3 +/- 1.3, P =.002, and N/M = 0.36 +/- 0.08 vs 0.17 +/- 0.03, P <.001).

CONCLUSION

hH(e) accelerates NH in a rat CCA balloon-injury model. The effect of hH(e) on NH may contribute to increased atherosclerosis in humans with hH(e).

摘要

目的

高同型半胱氨酸血症（hH[e]）是动脉粥样硬化的一个危险因素。血管损伤后的内膜增生（NH）可促使动脉粥样硬化的发生。在本研究中，我们调查了hH(e)对大鼠动脉球囊损伤后NH形成的影响。

方法

将给予hH(e)诱导饮食（高蛋氨酸、低叶酸）或正常饮食150天的Lewis大鼠行颈总动脉（CCA）球囊损伤。损伤后2周和4周，将CCA用福尔马林灌注固定、切片并进行弹性蛋白染色。使用计算机辅助显微镜测量内膜指数（NI，管腔闭塞百分比）以及内膜（N）和中膜（M）面积。

结果

与给予正常饮食的大鼠相比，给予研究饮食的大鼠在第40天和第90天时血浆同型半胱氨酸（H[e]）水平升高（69±8和73±9 μmol/L vs 4±0.4和4±0.6 μmol/L，P<.001）。球囊损伤后，与正常血浆H(e)水平相比，hH(e)使CCA的NI和N/M比值升高，但M面积未升高（2周[n = 6,7]：NI = 7.3±1.7 vs 2.9±0.7，P =.002，N/M = 0.31±0.08 vs 0.08±0.02，P<.001；4周[n = 4,7]：NI = 13.1±2.2 vs 6.3±1.3，P =.002，N/M = 0.36±0.08 vs 0.17±0.03，P<.001）。