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应用宽场成像和常规免疫组织化学检测技术对诱导性糖尿病的临床前模型中受损的伤口愈合进行特征描述。

Characterisation of impaired wound healing in a preclinical model of induced diabetes using wide-field imaging and conventional immunohistochemistry assays.

机构信息

The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.

Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California.

出版信息

Int Wound J. 2019 Feb;16(1):144-152. doi: 10.1111/iwj.13005. Epub 2018 Oct 1.

Abstract

Major complications of diabetes lead to inflammation and oxidative stress, delayed wound healing, and persistent ulcers. The high morbidity, mortality rate, and associated costs of management suggest a need for non-invasive methods that will enable the early detection of at-risk tissue. We have compared the wound-healing process that occurs in streptozotocin (STZ)-treated diabetic rats with non-diabetic controls using contrast changes in colour photography (ie, Weber Contrast) and the non-invasive optical method Spatial Frequency Domain Imaging (SFDI). This technology can be used to quantify the structural and metabolic properties of in-vivo tissue by measuring oxyhaemoglobin concentration (HbO ), deoxyhaemoglobin concentration (Hb), and oxygen saturation (StO ) within the visible boundaries of each wound. We also evaluated the changes in inducible nitric oxide synthase (iNOS) in the dermis using immunohistochemistry. Contrast changes in colour photographs showed that diabetic rats healed at a slower rate in comparison with non-diabetic control, with the most significant change occurring at 7 days after the punch biopsy. We observed lower HbO , StO , and elevated Hb concentrations in the diabetic wounds. The iNOS level was higher in the dermis of the diabetic rats compared with the non-diabetic rats. Our results showed that, in diabetes, there is higher level of iNOS that can lead to an observed reduction in HbO levels. iNOS is linked to increased inflammation, leading to prolonged wound healing. Our results suggest that SFDI has potential as a non-invasive assessment of markers of wound-healing impairment.

摘要

糖尿病的主要并发症会导致炎症和氧化应激、伤口愈合延迟和持续溃疡。高发病率、死亡率和相关管理成本表明需要非侵入性方法,以便能够早期发现有风险的组织。我们比较了链脲佐菌素(STZ)处理的糖尿病大鼠和非糖尿病对照动物的伤口愈合过程,使用了颜色摄影(即 Weber 对比)和非侵入性光学方法空间频域成像(SFDI)的对比变化。该技术可通过测量每个伤口可见边界内的氧合血红蛋白浓度(HbO )、脱氧血红蛋白浓度(Hb)和氧饱和度(StO ),用于量化体内组织的结构和代谢特性。我们还使用免疫组织化学评估真皮中诱导型一氧化氮合酶(iNOS)的变化。彩色照片的对比变化表明,与非糖尿病对照相比,糖尿病大鼠的愈合速度较慢,在穿刺活检后 7 天发生了最显著的变化。我们观察到糖尿病伤口中的 HbO 、StO 较低,Hb 浓度升高。与非糖尿病大鼠相比,糖尿病大鼠真皮中的 iNOS 水平更高。我们的结果表明,在糖尿病中,iNOS 水平升高会导致观察到的 HbO 水平降低。iNOS 与炎症增加有关,导致伤口愈合延长。我们的结果表明,SFDI 具有作为伤口愈合受损的非侵入性评估标志物的潜力。

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