Tsuruoka Takuya, Kodama Akio, Yamaguchi Shukuro, Masutomi Tomohiro, Koyama Akio, Murohara Toyoaki, Komori Kimihiro, Shibata Rei
Division of Vascular and Endovascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
JVS Vasc Sci. 2021 Dec 8;3:30-40. doi: 10.1016/j.jvssci.2021.09.023. eCollection 2022.
Zinc is an important essential trace metal involved in many physiologic functions, and its deficiency can affect the development of multiple organs, including the vasculature. However, clarity is lacking regarding the effects of zinc deficiency in the regulation of angiogenesis. We investigated the effects of zinc deficiency on the revascularization process through animal experiments and examined the relationship between the circulating zinc levels and tissue blood perfusion in patients with chronic limb-threatening ischemia (CLTI).
Zinc-deficient mice and control wild-type mice had undergone surgery to create unilateral hindlimb ischemia. Next, we examined the relationship between the serum zinc levels and skin perfusion pressure (SPP) as an index of tissue blood perfusion in patients with CLTI. A total of 51 patients with CLTI who had been referred for de novo revascularization for CLTI due to arteriosclerosis obliterans at our hospital from May 2012 to March 2016 were enrolled.
The zinc-deficient mice showed a significant reduction in blood flow recovery rates in the ischemic limb and capillary density in the ischemic adductor muscle fibers compared with the control wild-type mice. The zinc-deficient mice also showed increased reactive oxygen species production after hindlimb ischemia. Nicotinamide adenine dinucleotide phosphate oxidase inhibitors ameliorated the zinc deficient-induced impairment of revascularization. The serum zinc levels were positively associated with the SPP in the CLTI patients. Multivariate regression analysis also revealed that the serum zinc levels were significantly correlated with the SPP in patients with CLTI.
Zinc deficiency impaired the rate of ischemia-induced revascularization through enhanced oxidative stress rates, suggesting that nutritional management for zinc sufficiency could be useful in CLTI prevention and treatment.
锌是一种参与多种生理功能的重要必需微量元素，其缺乏会影响包括脉管系统在内的多个器官的发育。然而，锌缺乏在血管生成调节中的作用尚不清楚。我们通过动物实验研究了锌缺乏对血管再生过程的影响，并检测了慢性肢体威胁性缺血（CLTI）患者循环锌水平与组织血流灌注之间的关系。
对缺锌小鼠和对照野生型小鼠进行手术以造成单侧后肢缺血。接下来，我们检测了CLTI患者血清锌水平与作为组织血流灌注指标的皮肤灌注压（SPP）之间的关系。纳入了2012年5月至2016年3月期间在我院因动脉硬化闭塞症首次接受CLTI血管重建治疗的51例CLTI患者。
与对照野生型小鼠相比，缺锌小鼠缺血肢体的血流恢复率和缺血内收肌纤维中的毛细血管密度显著降低。缺锌小鼠在后肢缺血后还表现出活性氧生成增加。烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂改善了锌缺乏诱导的血管再生损伤。CLTI患者的血清锌水平与SPP呈正相关。多变量回归分析还显示，CLTI患者的血清锌水平与SPP显著相关。
锌缺乏通过提高氧化应激率损害了缺血诱导的血管再生速率，这表明充足的锌营养管理可能有助于CLTI的预防和治疗。
