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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb.
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Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb.

机译：自体骨髓细胞疗法和代谢干预在小鼠后肢缺血诱导的血管新生中的有益作用。

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摘要

Lower-limb ischemia is a major health problem. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include the intramuscular use of autologous bone marrow cells (BMCs). Because tissue ischemia is associated with an overwhelming generation of oxygen radicals and negative effects due to perturbed shear-stress, metabolic intervention with antioxidants and l-arginine could potentially induce beneficial effects beyond those achieved by BMCs. The protective effect of autologous BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute peripheral arterial occlusion. i.v. BMC therapy improved blood flow and increased capillary densities and expression of Ki-67, a proliferation-associated protein. Thisbeneficial effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation. Therefore, although a cautious approach is mandatory when experimental findings are extended to human diseases, autologous BMCs together with metabolic intervention could be an effective clinical treatment for peripheral arterial disease.
机译：下肢缺血是主要的健康问题。由于在疾病的晚期阶段缺乏有效的治疗方法，因此采取截肢术以减轻难以忍受的症状。新颖的治疗方法包括肌内使用自体骨髓细胞（BMC）。由于组织缺血与氧自由基的大量产生和剪切应力的扰动引起的负面影响有关，因此抗氧化剂和1-精氨酸的代谢干预可能会产生超出BMC所产生的有益作用。在小鼠后肢缺血诱导的血管新生中，研究了自体BMC的保护作用和通过代谢共处理（向食物中添加1.0％维生素E，向饮用水中添加0.05％维生素C和6％l-精氨酸）的血管保护作用，广泛的急性周围动脉阻塞模型。 i.v. BMC治疗改善了血流，增加了毛细血管的密度，并增加了与增殖相关的蛋白Ki-67的表达。这种有益作用通过代谢共处理得到了增强，代谢共处理是一种至少部分通过一氧化氮途径，减少全身性氧化应激和巨噬细胞活化来诱导血管保护的干预措施。因此，尽管在将实验结果扩展到人类疾病时必须采取谨慎的方法，但自体BMC与代谢干预一起可能是外周动脉疾病的有效临床治疗方法。

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