后肢跛行反映了缺血后一氧化氮依赖性血管再生受损。

Hindlimb claudication reflects impaired nitric oxide-dependent revascularization after ischemia.

作者信息

Luque Contreras Diana, Jiménez Estrada Ismael, Martínez Fong Daniel, Segura Bertha, Guadarrama José Carlos, Paniagua Sierra Ramón, Vargas Robles Hilda, Rios Amelia, Escalante Bruno

机构信息

Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, Colonia San Pedro Zacatenco, México City, Mexico.

出版信息

Vascul Pharmacol. 2007 Jan;46(1):10-5. doi: 10.1016/j.vph.2006.06.017. Epub 2006 Aug 14.

DOI:10.1016/j.vph.2006.06.017

PMID:17011243

Abstract

Although vascular remodeling is important in preventing tissue damage and restoring muscle function, there is no evidence of a relationship between vascular remodeling and muscle function after peripheral vascular occlusion. Nitric oxide (NO) has been implicated in the process of vascular remodeling in hindlimb ischemia. Thus, development of alterations in hindlimb gait after ischemia may be associated with impaired nitric oxide-dependent, vascular blood flow recovery. We evaluated hindlimb gait as an index of ischemia-induced revascularization and tested the effects of NO synthase inhibition on both hindlimb blood flow and hindlimb gait locomotion. After 14 days of ischemia, the ischemic hindlimb showed no significant differences in gait locomotion compared to the sham-operated hindlimb. However, hindlimb ischemia drastically reduced hindlimb blood flow from 46+/-3 mL/min/100 g to 12+/-2 mL/min/100 g which reverted to 33+/-5 mL/min/100 g after 14 days of ischemia. eNOS mRNA expression levels at 3, 7, 14, and 28 days after initiation of ischemia, were increased by 50+/-5%, 100+/-10%, 140+/-8% and 270+/-12% respectively and eNOS protein expression levels at 7, 14, and 28 days, were increased by 28+/-3%, 62+/-6% and 80+/-16% respectively. However, eNOS inhibition caused by l-NAME treatment prevented blood flow recovery and correction of abnormal gait locomotion in rats. Thus, the duration of the stride-swing phase increased and the stride length decreased. The knee joint angle decreased during flexion and extension with eNOS inhibition. In conclusion, ischemia-induced revascularization is associated with recovery of both hindlimb blood flow and normal gait locomotion. Moreover, prevention of NO synthesis, a key messenger in ischemia-induced revascularization, is associated with impairment in hindlimb locomotion. Thus, gait locomotion represents a functional model that could be used to evaluate the degree of ischemia-induced revascularization.

摘要

尽管血管重塑在预防组织损伤和恢复肌肉功能方面很重要，但在外周血管闭塞后，没有证据表明血管重塑与肌肉功能之间存在关联。一氧化氮（NO）与后肢缺血时的血管重塑过程有关。因此，缺血后后肢步态改变的发生可能与一氧化氮依赖性血管血流恢复受损有关。我们将后肢步态作为缺血诱导的血管再形成的指标进行评估，并测试了一氧化氮合酶抑制对后肢血流和后肢步态运动的影响。缺血14天后，与假手术的后肢相比，缺血后肢在步态运动方面没有显著差异。然而，后肢缺血使后肢血流从46±3毫升/分钟/100克急剧减少至12±2毫升/分钟/100克，在缺血14天后又恢复至33±5毫升/分钟/100克。缺血开始后3天、7天、14天和28天的内皮型一氧化氮合酶（eNOS）mRNA表达水平分别增加了50±5%、100±10%、140±8%和270±12%，而在7天、14天和28天的eNOS蛋白表达水平分别增加了28±3%、62±6%和80±16%。然而，L-精氨酸甲酯（l-NAME）处理引起的eNOS抑制阻止了大鼠的血流恢复和异常步态运动的纠正。因此，步幅摆动期的持续时间增加，步幅长度减小。eNOS抑制时，膝关节在屈伸过程中的角度减小。总之，缺血诱导的血管再形成与后肢血流恢复和正常步态运动均相关。此外，一氧化氮合成的阻断（缺血诱导的血管再形成中的关键信使）与后肢运动障碍有关。因此，步态运动代表了一个可用于评估缺血诱导的血管再形成程度的功能模型。