依那西普在大鼠模型中保护卵巢储备免受缺血/再灌注损伤。
Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model.
作者信息
Eken Meryem Kurek, Ersoy Gulcin Sahin, Kaygusuz Ecmel Işık, Devranoğlu Belgin, Takır Mümtaz, Çilingir Özlem Tuğçe, Çevik Özge
机构信息
Obstetrics and Gynecology Department, Medical Faculty, Adnan Menderes University, Aydın, Turkey.
Obstetric and Gynecology Department, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul, Turkey.
出版信息
Arch Med Sci. 2019 Jul;15(4):1104-1112. doi: 10.5114/aoms.2017.72406. Epub 2019 Feb 25.
INTRODUCTION
Etanercept has been widely used in autoimmune diseases for blocking tumor necrosis factor α (TNF-α), which is an inflammatory cytokine. The anti-apoptotic and anti-inflammatory effects of etanercept against ischemia/reperfusion (I/R) injury have been shown for several tissues in rat studies, but to the best of our knowledge, there are no reports on its protective effects following similar injury in ovarian tissue. The aim of this study was to investigate whether etanercept has beneficial effects on ovarian I/R injury, as well as on ovarian reserve.
MATERIAL AND METHODS
Twenty-four rats were randomly divided into four groups ( = 6/group): sham (laparotomy only); sham + etanercept; I/R; and I/R + etanercept. Ischemia was induced for 3 h by twisting the ovary, and 24 h after detorsion the ovarian tissues were collected to evaluate histopathologic changes, glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) concentrations for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, caspase-3 activity for apoptosis and ovarian follicle counts. To measure anti-Mullerian hormone (AMH), serum samples were drawn before and after surgery.
RESULTS
Tissue GSH and SOD levels were significantly higher, while MDA and MPO levels were significantly lower in the I/R + etanercept group than in the I/R group ( < 0.05, < 0.01, respectively). Tissue 8-OHdG and caspase-3 activity were significantly lower in the I/R+etanercept group than in the I/R group ( < 0.05, < 0.01, respectively). Preoperative and postoperative AMH levels were compared and there was a significant reduction in the I/R and I/R + etanercept groups ( < 0.001, < 0.001). The reduction of AMH in the I/R + etanercept group was significantly lower than in the I/R group. The primordial, preantral and small antral follicle numbers were also significantly higher in the I/R + etanercept group compared to the I/R group ( < 0.001 < 0.001, < 0.005, respectively).
CONCLUSIONS
Etanercept attenuated inflammation and related oxidative stress and also helped to preserve ovarian reserve following ovarian I/R damage.
引言
依那西普已广泛用于自身免疫性疾病，用于阻断炎症细胞因子肿瘤坏死因子α（TNF-α）。在大鼠研究中，依那西普对多种组织的缺血/再灌注（I/R）损伤具有抗凋亡和抗炎作用，但据我们所知，尚无关于其对卵巢组织类似损伤后保护作用的报道。本研究的目的是探讨依那西普对卵巢I/R损伤以及卵巢储备是否具有有益作用。
材料与方法
将24只大鼠随机分为四组（每组 = 6只）：假手术组（仅行剖腹术）；假手术 + 依那西普组；I/R组；I/R + 依那西普组。通过扭转卵巢诱导缺血3小时，扭转解除后24小时收集卵巢组织，以评估组织病理学变化、谷胱甘肽（GSH）、丙二醛（MDA）、髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）浓度以检测氧化应激，8-羟基-2'-脱氧鸟苷（8-OHdG）检测DNA损伤，半胱天冬酶-3活性检测细胞凋亡以及卵巢卵泡计数。为检测抗苗勒管激素（AMH），在手术前后采集血清样本。
结果
I/R + 依那西普组的组织GSH和SOD水平显著高于I/R组，而MDA和MPO水平显著低于I/R组（分别为 < 0.05， < 0.01）。I/R + 依那西普组的组织8-OHdG和半胱天冬酶-3活性显著低于I/R组（分别为 < 0.05， < 0.01）。比较术前和术后AMH水平，I/R组和I/R + 依那西普组均有显著降低（ < 0.001， < 0.001）。I/R + 依那西普组AMH的降低显著低于I/R组。与I/R组相比，I/R + 依那西普组的原始卵泡、窦前卵泡和小窦卵泡数量也显著更高（分别为 < 0.001 < 0.001， < 0.005）。
结论
依那西普减轻了炎症及相关氧化应激，并且有助于在卵巢I/R损伤后保护卵巢储备。
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