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分娩中 CB 大麻素受体和大麻素受体相互作用蛋白 1a 的差异表达

Differential Expression of CB Cannabinoid Receptor and Cannabinoid Receptor Interacting Protein 1a in Labor.

机构信息

Section on Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

出版信息

Cannabis Cannabinoid Res. 2022 Jun;7(3):279-288. doi: 10.1089/can.2020.0107. Epub 2021 Apr 16.

Abstract

The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann-Whitney test. Immunohistochemistry demonstrated positive staining for CB cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (=0.06). mRNA expression of CB cannabinoid receptor (=0.20) and CRIP1a (=0.63) did not differ in labored compared with nonlabored uterine tissues. Our findings of diminished protein density of CB cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

摘要

内源性大麻素系统存在于多个器官系统中,参与平滑肌调节、免疫功能、神经内分泌调节以及组织代谢。关于该系统在生殖组织中的存在和作用,目前仅有有限的数据。内源性大麻素系统的成分已在子宫和胎盘组织中被鉴定出来。然而,目前尚无研究调查内源性大麻素系统在分娩中的差异表达。本研究的目的是鉴定和量化内源性大麻素系统的两个成分,即 CB 大麻素受体和大麻素受体相互作用蛋白 1a(CRIP1a),在子宫和胎盘组织中的表达,并确定其在暴露于分娩的组织中的差异表达。我们假设与未暴露于分娩的组织相比,暴露于分娩的子宫和胎盘组织中的 CB 大麻素受体浓度会发生改变。本研究共纳入 9 名分娩和 11 名非分娩的行剖宫产术的女性,采集其子宫和胎盘组织样本。采用 Western blot、免疫组织化学和实时定量聚合酶链反应评估 CB 大麻素受体和 CRIP1a 的存在和定量。采用 Mann-Whitney 检验比较分娩和非分娩患者的子宫和胎盘组织的统计学差异。免疫组织化学显示 CB 大麻素受体和 CRIP1a 在子宫组织中呈阳性染色。暴露于分娩的子宫组织中 CB 大麻素受体的蛋白丰度明显较低(=0.01)。暴露于分娩的子宫组织中 CRIP1a 的蛋白丰度较低,但未达到统计学意义(=0.06)。与非分娩的子宫组织相比,分娩的子宫组织中 CB 大麻素受体(=0.20)和 CRIP1a(=0.63)的 mRNA 表达无差异。本研究发现,暴露于分娩的子宫组织中 CB 大麻素受体的蛋白密度降低,这支持了内源性大麻素系统在分娩中发挥作用的假说。本研究结果进一步证实了内源性大麻素系统对生殖成功的重要性,并支持需要进一步研究这一复杂系统与分娩的关系。ClinicalTrials.gov ID:NCT03752021。

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