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内源性大麻素家族成员失调在子宫内膜异位症病理生理学中的意义。

Implications of dysregulated endogenous cannabinoid family members in the pathophysiology of endometriosis.

机构信息

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Department of Pathology and Molecular Medicine, Kingston Health Sciences Center, Kingston, Ontario, Canada.

出版信息

F S Sci. 2021 Nov;2(4):419-430. doi: 10.1016/j.xfss.2021.09.005. Epub 2021 Oct 6.

DOI:10.1016/j.xfss.2021.09.005
PMID:35559864
Abstract

OBJECTIVE

To determine the involvement of the endocannabinoid (EC) family member in the pathophysiology of endometriosis (EMS).

DESIGN

Mass spectrometry analysis of plasma and tissue samples from patients with EMS, controls, and a mouse model of EMS and messenger RNA and immunohistochemistry analysis of the samples from patients with EMS and controls.

SETTING

Academic teaching hospital and university.

PATIENT(S): Patients with EMS and healthy fertile control subjects.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Endocannabinoid analysis in patient plasma, EMS lesions, and healthy endometrial samples.

RESULT(S): Circulating ECs were detected in the plasma samples, whereas no significant changes were observed in patients with EMS compared with healthy fertile controls. However, the palmitoylethanolamide levels were significantly higher in the EMS lesions than in the endometrium from patients with EMS. Similarly, genes involved in the EC signaling pathways were differentially expressed in the EMS lesions. Analysis of cannabinoid 1 and 2 receptors in the EMS lesions revealed a significantly lower cannabinoid 2 receptor expression, whereas no significant changes were observed in cannabinoid 1 receptor expression compared with those in the endometrium from both patients with EMS and healthy fertile controls. The palmitoylethanolamide levels were significantly elevated in plasma from EMS mice compared with that from sham controls and in EMS lesions compared with uterine samples.

CONCLUSION(S): Together, we provide evidence toward dysregulation of members of the ECs in both patients with EMS and the mouse model of EMS. These findings will advance the knowledge of the role of ECs in EMS and their potential implications as therapeutic targets.

摘要

目的

确定内源性大麻素(EC)家族成员在子宫内膜异位症(EMS)病理生理学中的作用。

设计

对 EMS 患者、对照者和 EMS 小鼠模型的血浆和组织样本进行质谱分析,对 EMS 患者和对照者的样本进行信使 RNA 和免疫组织化学分析。

地点

学术教学医院和大学。

患者

EMS 患者和健康有生育能力的对照者。

干预措施

无。

主要观察指标

患者血浆、EMS 病变和健康子宫内膜样本中的内源性大麻素分析。

结果

在血浆样本中检测到循环 ECs,而与健康有生育能力的对照者相比,EMS 患者无明显变化。然而,在 EMS 病变中,棕榈酰乙醇酰胺水平明显高于 EMS 患者的子宫内膜。同样,EC 信号通路相关基因在 EMS 病变中表达不同。在 EMS 病变中分析大麻素 1 和 2 受体发现,大麻素 2 受体表达明显降低,而与 EMS 患者和健康有生育能力的对照者的子宫内膜相比,大麻素 1 受体表达无明显变化。与 sham 对照相比,EMS 小鼠的血浆中棕榈酰乙醇酰胺水平明显升高,与子宫样本相比,EMS 病变中的棕榈酰乙醇酰胺水平也明显升高。

结论

综上所述,我们提供了证据表明,EC 成员在 EMS 患者和 EMS 小鼠模型中均失调。这些发现将推进对 EC 在 EMS 中的作用及其作为治疗靶点的潜在意义的认识。

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