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单核细胞表型作为糖尿病相关足部溃疡伤口愈合的预测标志物

Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers.

作者信息

Min Danqing, Nube Vanessa, Tao Anh, Yuan Xin, Williams Paul F, Brooks Belinda A, Wong Jencia, Twigg Stephen M, McLennan Susan V

机构信息

Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School (Central), Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

出版信息

J Diabetes Complications. 2021 May;35(5):107889. doi: 10.1016/j.jdiacomp.2021.107889. Epub 2021 Feb 16.

Abstract

AIMS

Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study.

METHODS

Blood was obtained from 21 participants with DRFU, at initial visit (V1), week-4 (V2), and week-8 (V3) for measurement of monocyte number (CD14), phenotype (CD16, CD163) and chemokine receptors (CCRs) by flow cytometry, and circulating MMPs and TIMP-1 by ELISA.

RESULTS

Six wounds healed during the study. At V1, non-classical CD16 monocytes and MMP-3 were higher in healed vs unhealed (both p < 0.05). At V3, the increased %CD16 persisted and %CCR2 was decreased in healed, but no other monocyte markers nor MMP/TIMP differed between groups. Increased wound closure rate (WCR) at V3 correlated with increased %CD16 monocytes and decreased MMP-2 at V1 or V1 + V2. Receiver operating characteristic (ROC) curves yielded an area-under-the-curve of %CD16 at V1 of 0.78 to predict ulcer healing at V3.

CONCLUSIONS

These results indicate that circulating monocyte phenotype and MMPs alter as DRFUs heal. The relationship of %CD16 monocytes with WCR and ROC curve suggest a predictive role of %CD16 monocytes for ulcer healing.

摘要

目的

糖尿病相关足部溃疡(DRFU)愈合延迟与伤口部位巨噬细胞和基质金属蛋白酶(MMP)增加有关。循环单核细胞表型和/或MMP是否会随着伤口愈合结果而改变尚不清楚,本研究对此进行了调查。

方法

从21名DRFU参与者处采集血液,分别在初次就诊(V1)、第4周(V2)和第8周(V3),通过流式细胞术检测单核细胞数量(CD14)、表型(CD16、CD163)和趋化因子受体(CCR),并通过酶联免疫吸附测定法检测循环MMP和组织金属蛋白酶抑制剂-1(TIMP-1)。

结果

在研究期间,6处伤口愈合。在V1时,愈合伤口组的非经典CD16单核细胞和MMP-3高于未愈合伤口组(均p<0.05)。在V3时,愈合伤口组中升高的CD16百分比持续存在,CCR2百分比降低,但两组之间的其他单核细胞标志物以及MMP/TIMP均无差异。V3时伤口闭合率(WCR)增加与V1或V1+V2时CD16单核细胞百分比增加和MMP-2降低相关。受试者工作特征(ROC)曲线显示,V1时CD16百分比的曲线下面积为0.78,可预测V3时溃疡愈合情况。

结论

这些结果表明,随着DRFU愈合,循环单核细胞表型和MMP会发生改变。CD16单核细胞百分比与WCR和ROC曲线的关系表明,CD16单核细胞百分比对溃疡愈合具有预测作用。

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