Gulcan Erim, Gulcan Aynur, Erbilen Enver, Toker Serdar
Hospital of Dumlupinar University, Department of Internal Medicine, Kutahya, Turkey.
Med Hypotheses. 2007;69(6):1313-5. doi: 10.1016/j.mehy.2007.03.022. Epub 2007 May 11.
Diabetic foot ulcers (DFUs) consist of an interaction of neuropathy, ischemia and infection. Neuropathy affects sensory, motor and autonomic pathways. Pathogenic factors for neuropathy include hyperglycemia, nonenzymatic glycosylation, oxidative stress, ischemic and hypoxic factors, nerve growth factor anomalies, activation of polyol pathway and immunologic abnormalities. All these factors are stated to contribute to microvascular disease and neural dysfunction. Peripheral neuropathy and ischemia combined with repetitive traumas can lead to diabetic foot ulceration. Fifteen percent of diabetic patients develop foot ulcers during their lifetime and nonhealing ulcers are responsible for 85% of nontraumatic lower extremity amputation. On the other hand, the treatment cost of foot disease in diabetic patients is estimated at $1 billion annually. When these conditions are considered, it is very important to design improved and novel strategies for treatment and prevention of diabetic foot disease. Lipid-lowering agents, such as statins, have been shown to prevent cardiovascular events in patients with diabetes. However, in addition, to preventing macrovascular diseases, statins may also be able to retard the progression of microvascular complications of diabetes. Statins alter the balance between vasodilatation and vasoconstriction in favor of vasodilatation by increasing nitric oxide (NO) synthesis, by downregulating endothelin 1 (ET-1) synthesis and reducing vascular response to angiotensin-2 (AT-2). These agents have been shown to augment cerebral blood flow by upregulating endothelial nitric oxide synthase (eNOs) and to reduce cerebral infarct size in a murine model of cerebral ischemia. In addition, recent in vivo and in vitro investigations have evidenced that statins have a favorable effect on diabetic peripheral neuropathy independent of its lipid-lowering effect by demonstrating restoration or preservation of microcirculation of the sciatic nerve. We hypothesized that statins can be useful for the prevention and treatment of diabetic foot. Possible mechanisms include the reduction of neuropathy and ischemia or through growth factors, the effectiveness of which has been shown for fracture healing in animal models.
糖尿病足溃疡（DFUs）是神经病变、缺血和感染相互作用的结果。神经病变会影响感觉、运动和自主神经通路。神经病变的致病因素包括高血糖、非酶糖基化、氧化应激、缺血和缺氧因素、神经生长因子异常、多元醇途径激活以及免疫异常。据说所有这些因素都会导致微血管疾病和神经功能障碍。周围神经病变和缺血加上反复创伤可导致糖尿病足溃疡。15%的糖尿病患者在其一生中会发生足部溃疡，而不愈合的溃疡占非创伤性下肢截肢的85%。另一方面，糖尿病患者足部疾病的治疗费用估计每年为10亿美元。考虑到这些情况，设计改进的新型糖尿病足病治疗和预防策略非常重要。他汀类等降脂药物已被证明可预防糖尿病患者的心血管事件。然而，除了预防大血管疾病外，他汀类药物还可能能够延缓糖尿病微血管并发症的进展。他汀类药物通过增加一氧化氮（NO）合成、下调内皮素1（ET-1）合成以及降低血管对血管紧张素-2（AT-2）的反应，改变血管舒张和血管收缩之间的平衡，使其有利于血管舒张。这些药物已被证明可通过上调内皮型一氧化氮合酶（eNOs）增加脑血流量，并在脑缺血小鼠模型中减小脑梗死面积。此外，最近的体内和体外研究表明，他汀类药物对糖尿病周围神经病变具有有益作用，其作用独立于降脂作用，可通过恢复或保留坐骨神经的微循环来证明。我们假设他汀类药物可用于预防和治疗糖尿病足。可能的机制包括减轻神经病变和缺血或通过生长因子，其有效性已在动物模型的骨折愈合中得到证明。
