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微小RNA-126:负压伤口治疗糖尿病伤口血管生成的一种有前景的生物标志物。

MicroRNA-126: a promising biomarker for angiogenesis of diabetic wounds treated with negative pressure wound therapy.

作者信息

Zhang Dong, Li Zonghuan, Wang Zheng, Zeng Fanwei, Xiao Weidong, Yu Aixi

机构信息

Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2019 Sep 3;12:1685-1696. doi: 10.2147/DMSO.S199705. eCollection 2019.

Abstract

BACKGROUND

Negative pressure wound therapy represents an effective therapy to treat nonhealing diabetic wounds by promoting angiogenesis, of which the mechanism hasn't been investigated thoroughly. Growing evidence suggests that miRNAs hold great potential to be clinical biomarkers, and miR-126 is an essential angiogenesis regulator in diabetic wound repair.

PURPOSE

Our study aims to explore the effect of NPWT on the expression of miR-126 in the wound tissue and plasma of diabetic rat models and the association between circulating miR-126 and two quantitative indexes of angiogenesis.

METHODS

Full-thickness excisional wounds were created on the back of diabetic rats. Measure the wound closure and collect the wound tissue and blood for H&E, immunohistochemistry, Western blot and RT-PCR. Here we demonstrated that significantly increased capillary density and arteriolar density in the NPWT group at each specified time-point.

RESULTS

In the NPWT group, miR-126 expression was significantly increased on days 3, 5, 7, and 9 (<0.05). Furthermore, statistically significant increases in VEGF mRNA and protein expression and p-ERK expression, as well as decreased SPRED1 expression, were noted upon treatment with NPWT on day 9. Our data revealed that miR-126 expression in the wound and plasma was significantly associated (<0.05). Moreover, a positive correlation was also detected between increased levels of circulating miR-126 and arteriolar density, as well as capillary density (<0.05).

CONCLUSION

The study suggested that miR-126 was upregulated by NPWT and could represent a promising monitoring tool for angiogenesis in diabetic wounds treated with NPWT.

摘要

背景

负压伤口治疗是一种通过促进血管生成来治疗难愈合糖尿病伤口的有效疗法,但其机制尚未得到充分研究。越来越多的证据表明,微小RNA有很大潜力成为临床生物标志物,而miR-126是糖尿病伤口修复中一种重要的血管生成调节因子。

目的

本研究旨在探讨负压伤口治疗对糖尿病大鼠模型伤口组织和血浆中miR-126表达的影响,以及循环miR-126与两个血管生成定量指标之间的关联。

方法

在糖尿病大鼠背部制造全层切除伤口。测量伤口愈合情况,并收集伤口组织和血液进行苏木精-伊红染色、免疫组织化学、蛋白质免疫印迹和逆转录-聚合酶链反应。我们在此证明,在每个指定时间点,负压伤口治疗组的毛细血管密度和小动脉密度显著增加。

结果

在负压伤口治疗组中,第3、5、7和9天时miR-126表达显著增加(<0.05)。此外,在第9天用负压伤口治疗后,观察到血管内皮生长因子mRNA和蛋白表达以及磷酸化细胞外信号调节激酶表达有统计学意义的增加,而Sprouty相关蛋白1表达降低。我们的数据显示,伤口和血浆中的miR-126表达显著相关(<0.05)。此外,还检测到循环miR-126水平升高与小动脉密度以及毛细血管密度之间呈正相关(<0.05)。

结论

该研究表明,负压伤口治疗可上调miR-126,它可能是监测负压伤口治疗糖尿病伤口血管生成的一种有前景的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa57/6732575/9c1a4015a999/DMSO-12-1685-g0001.jpg

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