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叶酸对大鼠子宫缺血再灌注损伤的保护作用:减轻炎症损伤和凋亡性死亡。

Protective effects of folic acid on ischemia‒reperfusion injury in rat uterus: reduces inflammation damage and apoptotic death.

作者信息

Paksoy Zahid, Yumusak Nihat

机构信息

Department of Veterinary Science, Elbistan Vocational School, Kahramanmaraş İstiklal University, Kahramanmaraş, Türkiye, Turkey.

Department of Pathology, Faculty of Veterinary Medicine, Harran University, Şanlıurfa, Türkiye, Turkey.

出版信息

BMC Vet Res. 2025 Jul 24;21(1):486. doi: 10.1186/s12917-025-04949-9.

Abstract

BACKGROUND

Uterine torsion is a pregnancy pathology that poses risks to both maternal and fetal health. This condition is closely associated with the relaxation of uterine ligaments due to hormonal changes and the increased size of the gravid uterus. It occurs when the uterus rotates around its own axis. This torsion can result in ischemia, and if untreated, may progress to necrosis and fetal loss. Folic acid has protective effects against oxidative stress, inflammation, and apoptosis. The aim of this study was to investigate the potential of folic acid to reduce ischemia‒reperfusion (IR) injury in the rat uterus.

RESULTS

IR caused severe edema, inflammation, congestion, hemorrhage, vasoconstriction, and necrosis in the uterus. Histopathological damage was less pronounced in rats treated with folic acid. Although the endometrial layer, critical for fertility, suffered significant damage, folic acid effectively prevented this injury. Immunohistochemical analysis revealed that caspase-3 activity, a marker of apoptosis, increased in response to IR. However, folic acid treatment attenuated this activity, and uterine inflammation also reduced. High-dose folic acid inhibited TNF-alpha immunoreactivity. Interestingly, folic acid did not activate antioxidant mechanisms to reduce oxidative stress. Nevertheless, it mitigated IR-induced damage by reducing endometrial injury and preventing inflammation and apoptosis.

CONCLUSIONS

As a result, uterine torsion can lead to endometrial damage, degeneration, inflammation, and apoptosis, potentially affecting fertility. High-dose folic acid treatment may protect the uterus from these damages, thereby preserving fertility. This study suggests that folic acid, particularly at high doses, may be safe and beneficial treatment to prevent IR damage and promote uterine health.

摘要

背景

子宫扭转是一种妊娠病理状况,对母体和胎儿健康均构成风险。这种情况与激素变化导致子宫韧带松弛以及妊娠子宫体积增大密切相关。它发生于子宫围绕自身轴线旋转时。这种扭转可导致局部缺血,若不治疗,可能进展为坏死和胎儿丢失。叶酸对氧化应激、炎症和细胞凋亡具有保护作用。本研究的目的是探讨叶酸减轻大鼠子宫缺血再灌注(IR)损伤的潜力。

结果

IR导致子宫严重水肿、炎症、充血、出血、血管收缩和坏死。叶酸治疗的大鼠组织病理学损伤较轻。尽管对生育至关重要的子宫内膜层遭受了显著损伤,但叶酸有效预防了这种损伤。免疫组织化学分析显示,作为细胞凋亡标志物的半胱天冬酶-3活性在IR后升高。然而,叶酸治疗减弱了这种活性,子宫炎症也减轻了。高剂量叶酸抑制肿瘤坏死因子-α免疫反应性。有趣的是,叶酸并未激活抗氧化机制来减轻氧化应激。尽管如此,它通过减轻子宫内膜损伤以及预防炎症和细胞凋亡减轻了IR诱导的损伤。

结论

因此,子宫扭转可导致子宫内膜损伤、退变、炎症和细胞凋亡,可能影响生育能力。高剂量叶酸治疗可能保护子宫免受这些损伤,从而维持生育能力。本研究表明,叶酸,尤其是高剂量叶酸,可能是预防IR损伤和促进子宫健康的安全有益的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65de/12288322/84863e987936/12917_2025_4949_Fig1_HTML.jpg

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