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基于转录组学的分析揭示了白藜芦醇对大鼠子宫内膜异位症的治疗作用。

Transcriptome-Based Analysis Reveals Therapeutic Effects of Resveratrol on Endometriosis in aRat Model.

机构信息

The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People's Republic of China.

Institute of Genetics, Zhejiang University; Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang Provincial Key Laboratory of Genetic & Developmental Disorders, Hangzhou, Zhejiang, 310058, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Sep 29;15:4141-4155. doi: 10.2147/DDDT.S323790. eCollection 2021.

Abstract

INTRODUCTION

Endometriosis (EMs) is associated with severe chronic pelvic pain and infertility and the development of improved EMs treatment options is an ongoing focus. In this study, we investigated the effects of resveratrol on EMs and analyzed transcriptional changes in the lesions of model rats before and after resveratrol treatment.

METHODS

We established arat model of endometriosis through the trans-implantation of endometrial fragments to the peritoneal wall and then used resveratrol as treatment. We then analyzed the results using RNA sequencing of the lesion tissues of each of the model rats before resveratrol treatment and the reduced lesion tissues after the treatment. Examinations of anatomy, biochemistry, immunohistochemical staining and flow cytometry examinations were also conducted. Other trans-implanted rats were also given sham treatments as sham-treatment control and other untrans-implanted rats served as sham-operation controls.

RESULTS

In addition to the obvious lesions observed in the model rats, there were significant differences in the glucose tolerance, macrophage M1/M2 polarization, and adipocyte sizes between the treated model rats and sham (control) rats. Resveratrol treatment in the model rats showed significant efficacy and positive therapeutic effect. Transcriptional analysis showed that the effects of resveratrol on the endometriosis model rats were manifested by alterations in the PPAR, insulin resistance, MAPK and PI3K/Akt signaling pathways. Correspondingly, changes in PPARγ activation, M1/M2 polarization and lipid metabolism were also detected after resveratrol treatment.

DISCUSSION

Our study revealed that resveratrol treatment displayed efficient therapeutic effects for EMs model rats, probably through its important roles in anti-inflammation, immunoregulation and lipid-related metabolism regulation.

摘要

简介

子宫内膜异位症(EMs)与严重的慢性盆腔疼痛和不孕有关,开发改进的 EMs 治疗方案是当前的重点。在这项研究中,我们研究了白藜芦醇对 EMs 的影响,并分析了白藜芦醇治疗前后模型大鼠病变组织中的转录变化。

方法

我们通过将子宫内膜碎片移植到腹膜壁上来建立大鼠子宫内膜异位症模型,然后用白藜芦醇进行治疗。然后,我们使用每个模型大鼠治疗前病变组织和治疗后减少的病变组织的 RNA 测序来分析结果。还进行了解剖学、生物化学、免疫组织化学染色和流式细胞术检查。其他移植的大鼠也接受了假手术治疗作为假手术对照,其他未移植的大鼠作为假手术对照。

结果

除了在模型大鼠中观察到明显的病变外,在治疗后的模型大鼠和假(对照)大鼠之间,葡萄糖耐量、巨噬细胞 M1/M2 极化和脂肪细胞大小存在显著差异。在模型大鼠中,白藜芦醇治疗显示出显著的疗效和积极的治疗效果。转录分析表明,白藜芦醇对子宫内膜异位症模型大鼠的作用是通过改变 PPAR、胰岛素抵抗、MAPK 和 PI3K/Akt 信号通路来实现的。相应地,在白藜芦醇治疗后还检测到 PPARγ 激活、M1/M2 极化和脂质代谢的变化。

讨论

我们的研究表明,白藜芦醇治疗对 EMs 模型大鼠显示出有效的治疗效果,可能是通过其在抗炎、免疫调节和脂质相关代谢调节中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/805d/8487867/956cf31420a2/DDDT-15-4141-g0001.jpg

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