Witte M B, Kiyama T, Barbul A
Departments of Surgery, Sinai Hospital of Baltimore and the Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Br J Surg. 2002 Dec;89(12):1594-601. doi: 10.1046/j.1365-2168.2002.02263.x.
Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes.
Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed.
OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes.
The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.
糖尿病的特征是伤口部位一氧化氮缺乏。本研究调查了用一氧化氮供体吗多明（N - 乙氧羰基 - 3 - 吗啉基 - 西多明）补充外源性一氧化氮是否能逆转糖尿病中受损的愈合过程。
通过在糖尿病大鼠和非糖尿病大鼠背部皮肤做切口并植入皮下聚乙烯醇海绵来研究伤口愈合情况。每组一半大鼠接受吗多明治疗。通过伤口抗张强度、羟脯氨酸（OHP）含量、I型和III型胶原蛋白的RNA表达以及伤口海绵中基质金属蛋白酶（MMP）2活性来评估胶原蛋白代谢。评估伤口液、血浆和尿液中一氧化氮代谢物水平以及炎症细胞数量。
吗多明显著提高了OHP含量和伤口抗张强度。糖尿病时伤口液中MMP - 2活性降低，一氧化氮供体使其上调。糖尿病中受损的炎症反应不受一氧化氮供体治疗影响，对照动物和糖尿病动物伤口巨噬细胞的体外一氧化氮合成无差异，这表明伤口中的一氧化氮缺乏是由于糖尿病中炎症反应较小。
一氧化氮供体吗多明至少可以部分逆转与糖尿病相关的愈合受损情况。
