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大麻素受体 2 型激动剂 JWH-133 对子宫缺血/再灌注损伤的保护作用。

The Activation of Cannabinoid Type-2 Receptor with JWH-133 Protects Uterine Ischemia/Reperfusion-Induced Damage.

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey,

Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.

出版信息

Pharmacology. 2021;106(1-2):106-113. doi: 10.1159/000511457. Epub 2020 Oct 26.

Abstract

INTRODUCTION

Uterus transplantation is a complex surgical procedure. Uterine ischemia/reperfusion (IR) damage occurring in this process may cause loss of function in the uterus. Cell damage must be prevented for a healthy uterine function and successful transplantation. Cannabinoids, with their increasing clinical use, are substances with strong anti-inflammatory and antioxidative effects and have a role in immune system regulation. However, their efficacy in uterine IR damage is still unknown. This study provides information on the potential applications cannabinoids agonist JWH-133 in uterine IR damage and, hence, in the transplant process.

METHODS

Rats were divided into 4 groups (n = 8), performed uterine IR, and treated 2 groups with JWH-133. After anesthesia, ischemia was applied for 1 h to the uterus while reperfusion was applied for 3 h. After the experiment, malondialdehyde (MDA) levels and phosphorylated nuclear factor-kappa B (p-NF-κB) expression were examined in the tissue samples. Also, cell damage was evaluated by histopathological imaging and TUNEL staining.

RESULTS

In the uterine IR group, NF-κB expression and MDA levels were detected at high levels. Histopathological examinations and TUNEL staining revealed extensive cell damage. On the other hand, in groups treated with JWH-133, dose-dependent NF-κB expression and MDA levels decreased (p < 0.05). Depending on the dose, the rate of surviving cells increased in TUNEL staining results.

CONCLUSION

The results showed that JWH-133 was effective in reducing uterine IR damage. Cannabinoids may be a new alternative that may be used in the transplantation process in the future.

摘要

简介

子宫移植是一项复杂的外科手术。该过程中发生的子宫缺血/再灌注(IR)损伤可能导致子宫功能丧失。为了实现健康的子宫功能和成功的移植,必须防止细胞损伤。大麻素具有越来越强的抗炎和抗氧化作用,并且在免疫系统调节中具有作用,随着其临床应用的增加,它们是具有强大抗炎和抗氧化作用的物质,并在免疫系统调节中具有作用。然而,它们在子宫 IR 损伤中的功效尚不清楚。本研究提供了有关大麻素激动剂 JWH-133 在子宫 IR 损伤中,从而在移植过程中的潜在应用的信息。

方法

将大鼠分为 4 组(n = 8),进行子宫 IR,并对 2 组用 JWH-133 进行治疗。麻醉后,子宫缺血 1 小时,再灌注 3 小时。实验结束后,检测组织样本中的丙二醛(MDA)水平和磷酸化核因子-κB(p-NF-κB)表达。还通过组织学成像和 TUNEL 染色评估细胞损伤。

结果

在子宫 IR 组中,检测到 NF-κB 表达和 MDA 水平升高。组织学检查和 TUNEL 染色显示广泛的细胞损伤。另一方面,用 JWH-133 治疗的组中,NF-κB 表达和 MDA 水平呈剂量依赖性降低(p <0.05)。在 TUNEL 染色结果中,取决于剂量,存活细胞的比例增加。

结论

结果表明 JWH-133 可有效减轻子宫 IR 损伤。大麻素可能是未来移植过程中的一种新的替代方法。

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