Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus
Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus
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DOI：
10.1006/jsre.2002.6525
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发表时间：
2002-11-01
影响因子：
2.2
通讯作者：
Olerud, JE
中科院分区：
文献类型：
--
作者：
Gibran, NS;Jang, YC;Olerud, JE
背景患有糖尿病感觉神经病变的患者具有显著的慢性溃疡风险。神经源性介质如P物质（SP）不足可能导致对损伤的反应受损。突变型糖尿病小鼠（db/db）可发生神经病变并延迟愈合，这可能为研究神经在皮肤损伤中的作用提供模型。对人类慢性不愈合溃疡皮肤和年龄匹配的对照皮肤进行神经化学评价。还比较了小鼠糖尿病（C57 BL/KsJ-m+/+ Lepr（db）; db/db）和非糖尿病（db/-）皮肤中的神经计数。将db/db和db/-小鼠背部的切除伤口分组为：（a）未处理的db/-小鼠;（B）未处理的db/db小鼠;（c）具有聚乙二醇（PEG）的db/db小鼠;（d）具有PEG和SP 10（-9）M的db/db小鼠;或（e）具有PEG和SP 10（-6）M的db/db小鼠。我们证明了较少的神经在表皮和乳头状真皮皮肤从人类受试者糖尿病。同样，db/db小鼠皮肤的表皮神经明显少于非糖尿病同窝小鼠。我们证实db/db小鼠（51.7天）与db/-同窝小鼠（19.8天; P小于或等于0.001）相比愈合时间增加。SP 10（-6）M（44天; P = 0.02）和SP 10（-9）M（45天; P = 0.03）与PEG单独治疗（68天）相比缩短了闭合时间。由于这些治疗组的收缩百分比没有差异，SP可能有利于促进伤口上皮化。我们的数据支持使用db/db小鼠切除伤口来评估神经在愈合中的作用。我们已经证明，外源性SP在动物模型中改善伤口愈合动力学。(C)2002 Elsevier Science（美国）。
Background. Patients with diabetic sensory neuropathy have significant risk of chronic ulcers. Insufficient nerve-derived mediators such as substance P (SP) may contribute to the impaired response to injury. Mutant diabetic mice (db/db), which develop neuropathy and have delayed healing, may provide a model to study the role of nerves in cutaneous injury.Methods. Skin from human chronic nonhealing ulcers and age-matched control skin was immunohistochemically evaluated for nerves. Nerve counts were also compared in murine diabetic (C57BL/KsJ-m+/+ Lepr(db); db/db) and nondiabetic (db/-) skin. Excisional wounds on the backs of db/db and db/- mice were grouped as: (a) untreated db/- mice; (b) untreated db/db mice; (c) db/db mice with polyethylene glycol (PEG); (d) db/db mice with PEG and SP 10(-9) M; or (e) db/db mice with PEG and SP 10(-6) M.Results. We demonstrated fewer nerves in the epidermis and papillary dermis of skin from human subjects with diabetes. Likewise, db/db murine skin had significantly fewer epidermal nerves than nondiabetic littermates. We confirmed increased healing times in db/db mice (51.7 days) compared to db/- littermates (19.8 days; P less than or equal to 0.001). SP 10(-6) M (44 days; P = 0.02) and SP 10(-9) M (45 days; P = 0.03) shortened time to closure compared to PEG treatment alone (68 days). Since there was no difference in the percentage contraction in these treatment groups, SP may favorably promote wound epithelization.Conclusions. Our data support the use of db/db murine excisional wounds to evaluate the role of nerves in healing. We have demonstrated that exogenous SP improves wound healing kinetics in an animal model. (C) 2002 Elsevier Science (USA).