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阿达木单抗通过调节氧化应激、细胞凋亡和炎症消退减轻大鼠卵巢缺血再灌注损伤。

Adalimumab mitigates ovarian ischemia-reperfusion injury in rats by regulating oxidative stress, apoptosis and resolution of inflammation.

作者信息

Beyazit Fatma, Büyük Başak, Turkon Hakan, Elmas Sait, Uzun Metehan

机构信息

Department of Obstetrics and Gynecology, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Department of Histology and Embryology, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

出版信息

J Obstet Gynaecol Res. 2019 Feb;45(2):358-367. doi: 10.1111/jog.13846. Epub 2018 Oct 24.

DOI:10.1111/jog.13846
PMID:30358007
Abstract

AIM

Ovarian torsion is a rare but an important reason of acute lower abdominal pain in women and associated with serious morbidity and mortality, if not treated promptly. The aim of this study was to evaluate the effects of an antitumor necrosis factor-α antibody on ovarian torsion in a rat model of ischemia-reperfusion (I/R) injury.

METHODS

Forty female Wistar Albino rats were used in the present study. The rats were randomly divided into four groups: group I (sham), group II (I/R), group III (I/R + isotonic saline) and group IV (I/R + adalimumab). The I/R model was induced by torsion of both ovaries. Immunohistochemical staining for interleukin-1β (IL-1β), nuclear factor-κB (NF-κB), and inducible nitric oxide synthase was performed. Tissue and serum oxidative stress markers in conjunction with apoptotic index (AI) with the terminal deoxynucleotidyl transferase dUTP nick end labeling method were also calculated.

RESULTS

Tissue total oxidant status, oxidative stress index and nitric oxide values were significantly decreased, and tissue total antioxidant status was found to be increased in group IV. Inflammation, vascular congestion and hemorrhagia were significantly lower in adalimumab-treated group. Serum oxidative stress markers and tissue malondialdehyde levels did not differ in study groups. The AI was significantly increased in groups 2 and 3. Adalimumab treatment significantly decreased the AI.

CONCLUSION

Adalimumab therapy in rats attenuated I/R induced ovarian injury, possibly suppressing inflammation, inhibiting oxidative stress, and altering apoptotic pathways.

摘要

目的

卵巢扭转是女性急性下腹痛的罕见但重要原因,若不及时治疗会导致严重的发病率和死亡率。本研究旨在评估抗肿瘤坏死因子-α抗体对缺血再灌注(I/R)损伤大鼠模型中卵巢扭转的影响。

方法

本研究使用了40只雌性Wistar白化大鼠。大鼠被随机分为四组:第一组(假手术组),第二组(I/R组),第三组(I/R +等渗盐水组)和第四组(I/R +阿达木单抗组)。通过扭转双侧卵巢诱导I/R模型。进行白细胞介素-1β(IL-1β)、核因子-κB(NF-κB)和诱导型一氧化氮合酶的免疫组织化学染色。还计算了组织和血清氧化应激标志物以及采用末端脱氧核苷酸转移酶dUTP缺口末端标记法的凋亡指数(AI)。

结果

第四组组织总氧化剂状态、氧化应激指数和一氧化氮值显著降低,且组织总抗氧化剂状态升高。阿达木单抗治疗组的炎症、血管充血和出血明显减轻。研究组之间血清氧化应激标志物和组织丙二醛水平无差异。第二组和第三组的AI显著升高。阿达木单抗治疗显著降低了AI。

结论

大鼠中的阿达木单抗治疗减轻了I/R诱导的卵巢损伤,可能是通过抑制炎症、抑制氧化应激和改变凋亡途径实现的。

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