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大麻二酚通过其在实验性大鼠模型中的抗炎、抗氧化和抗血管生成作用,成为治疗子宫内膜异位症的一种有潜力的新型治疗方法。

Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model.

机构信息

Acibadem Health Group, Department of Obstetrics, Gynecology and Reproductive Medicine, Acibadem Kozyatagi Hospital, Istanbul, Turkey.

Faculty of Medicine, Department of Obstetrics and Gynecology, Bezmialem University, Istanbul, Turkey.

出版信息

Reprod Biomed Online. 2023 May;46(5):865-875. doi: 10.1016/j.rbmo.2023.01.018. Epub 2023 Feb 2.

DOI:10.1016/j.rbmo.2023.01.018
PMID:36997400
Abstract

RESEARCH QUESTION

Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects?

DESIGN

Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.

RESULTS

Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-α (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-α (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group.

CONCLUSION

Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis.

摘要

研究问题

大麻二酚(CBD)能否通过其抗炎、抗氧化和抗血管生成作用用于子宫内膜异位症的治疗?

设计

通过手术在 36 只雌性 Wistar 白化大鼠中诱导子宫内膜植入物。在确认子宫内膜异位病灶后,将大鼠随机分为四组。在醋酸亮丙瑞林组中,大鼠给予单次 1mg/kg 皮下注射醋酸亮丙瑞林。其他组分别给予 5mg/kg CBD(CBD5)、生理盐水和 20mg/kg CBD(CBD20);每日腹腔注射给药 7 天。21 天后,处死大鼠,评估血液和腹腔液样本中的总抗氧化状态(TAS)、总氧化状态(TOS)、氧化应激指数(OSI)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,以及子宫内膜异位组织中 TNF-α、IL-6 和血管内皮生长因子(VEGF)的免疫组织化学染色。

结果

与生理盐水组相比,CBD5 组的子宫内膜植入物表面积显著减少(P=0.0213),血清 TOS(P=0.0491)、OSI(P=0.0056)、IL-6(P=0.0236)、TNF-α(P=0.0083)和腹腔液 OSI(P=0.0401)、IL-6(P=0.0205)和 TNF-α(P=0.0045)浓度均降低。与生理盐水组相比,CBD5 组血清(P=0.0012)和腹腔液(P=0.0145)中的 TAS 浓度增加。与生理盐水组相比,CBD5 组和醋酸亮丙瑞林组的血清和腹腔液样本的炎症和氧化应激参数相似。与醋酸亮丙瑞林组相比,CBD5 组的 VEGF 表面上皮和基质细胞的平均强度均显著降低(均 P=0.002),且仅在表面上皮细胞中 IL-6 的平均强度降低(P=0.0108)。

结论

由于 CBD 具有抗炎、抗氧化和抗血管生成作用,因此它可能是子宫内膜异位症的治疗候选药物。

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