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评价载蜂胶聚(乳酸-共-乙醇酸)纳米粒子的生物合成醇提取物对糖尿病大鼠伤口愈合的影响。

Evaluation of Effect of Biologically Synthesized Ethanolic Extract of Propolis-Loaded Poly(-Lactic-co-Glycolic Acid) Nanoparticles on Wound Healing in Diabetic Rats.

机构信息

Department of Pathology, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran.

Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

出版信息

Int J Low Extrem Wounds. 2024 Dec;23(4):513-523. doi: 10.1177/15347346211073224. Epub 2022 Jan 10.

Abstract

Wound healing is interaction of a complex cascade of cellular/biochemical actions leading to restoration of structural and functional integrity with regain of injured tissues strength. This study was aimed at evaluation of application of ethanolic extract of propolis-loaded poly(-lactic-co-glycolic acid) nanoparticles (EEP-PLGA NPs) on wound healing in diabetic rats. Sixty rats were randomized into four groups of 15 rats each: In control group (Control) diabetic wound was treated with normal saline. In Carrier 1 group diabetic wound was treated with PLGA nanoparticles based solution. In Carrier 2 group the diabetic wound was treated with EEP. In Treatment group animals received EEP-PLGA NPs on the wound. Wound size was measured on 7, 14 and 21 days after surgery. The expression of p53, bcl-2, Caspase III, were evaluated using reverse-transcription PCR and Immunohistochemical staining. The Treatment group had significantly reduced the wound size compared to other groups ( = 0.001). histological and morphometric studies, and mean rank of the qualitative studies demonstrated that there was significant difference between Treatment group and other groups ( < .05). Observations demonstrated that ethanolic extract of propolis-loaded PLGA nanoparticles significantly shortened the inflammatory phase and accelerated the cellular proliferation. Accordingly, the animals in Treatment group revealed significantly (< .05) higher fibroblast distribution/one mm of wound area and rapid re epithelialization. The mRNA levels of bcl-2, p53 and caspase III were remarkably (< .05) higher in Treatment group compared to control and animals. The immunohistochemical analyzes confirmed the RT-PCR findings. EEP-PLGA NPs offered potential advantages in wound healing acceleration and improvement through angiogenesis stimulation, fibroblast proliferation and granulation tissue formation in early days of healing phases, acceleration in diabetic wound repair associated with earlier wound contraction and stability of damaged area by rearrangement of granulation tissue and collagen fibers.

摘要

伤口愈合是一个复杂的细胞/生化级联反应的相互作用,导致结构和功能完整性的恢复以及受损组织强度的恢复。本研究旨在评估载有蜂胶乙醇提取物的聚(丙交酯-共-乙交酯)纳米粒子(EEP-PLGA NPs)在糖尿病大鼠伤口愈合中的应用。60 只大鼠随机分为 4 组,每组 15 只:对照组(Control)糖尿病伤口用生理盐水处理。载体 1 组糖尿病伤口用 PLGA 纳米粒子溶液处理。载体 2 组糖尿病伤口用 EEP 处理。治疗组动物在伤口上接受 EEP-PLGA NPs 治疗。术后第 7、14 和 21 天测量伤口大小。使用逆转录 PCR 和免疫组织化学染色评估 p53、bcl-2、Caspase III 的表达。与其他组相比,治疗组的伤口大小明显减小(=0.001)。组织学和形态计量学研究以及定性研究的平均等级表明,治疗组与其他组之间存在显著差异(<0.05)。观察结果表明,载有蜂胶乙醇提取物的 PLGA 纳米粒子显著缩短了炎症期并加速了细胞增殖。因此,治疗组动物表现出明显更高的成纤维细胞分布/每毫米伤口面积(<0.05)和快速再上皮化。与对照组和动物相比,治疗组 bcl-2、p53 和 caspase III 的 mRNA 水平明显升高(<0.05)。免疫组织化学分析证实了 RT-PCR 的发现。EEP-PLGA NPs 通过刺激血管生成、促进成纤维细胞增殖和肉芽组织形成,在愈合早期加速伤口愈合,并改善愈合,加速糖尿病伤口修复,通过加速伤口收缩和受损区域的稳定性来实现,通过肉芽组织和胶原纤维的重新排列来实现。

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