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瘦素通过调节 Sirt-1/Nrf2 和 TLR4/NF-κB/caspase-3 信号通路减轻大鼠卵巢缺血再灌注损伤。

Leptin alleviated ovarian ischemia-reperfusion injury in rats via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways.

机构信息

Medical Physiology Department, Faculty of Medicine, Minia University, Minia, Egypt.

Medical Physiology Department, Faculty of Medicine, Al-Baha University, KSA.

出版信息

Endocr Regul. 2023 Feb 8;57(1):25-36. doi: 10.2478/enr-2023-0004. Print 2023 Jan 1.

DOI:10.2478/enr-2023-0004
PMID:36753665
Abstract

Ovarian torsion is a gynecological emergency that occurs mostly during the female reproductive years due to ovarian masses or surgical manipulation. This work aims to explore the probable protective effect of leptin on rat ovaries due to ischemia-reperfusion (IR) injury. Wistar albino rats were divided into four groups: 1) control group; 2) ovarian IR group (OVIR); 3) leptin group I [OVIR + leptin (10 µg/kg body weight, b.w.)]; and 4) leptin group II (OVIR + leptin (100 µg/kg b.w.)]. Serum levels of estradiol and anti-Mullerian hormone (AMH) were measured. Levels of oxidative stress and inflammatory markers in ovarian tissue were determined along with the expression of sirtuin 1 (Sirt1), nuclear erythroid factor-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa (NF-κB), toll like receptor-4 (TLR4), and caspase-3. Serum estradiol and AMH levels were decreased with increased expression of COX-2, TLR4, caspase-3, and NF-κB and decreased expression of Sirt1and Nrf2 in ovary of the OVIR group, which were improved by exogenous administration of both leptin doses. Leptin administration dose-dependently reduced the severity of OVIR injury via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways. Thus, leptin may be used as an adjuvant measure to prevent ovarian damage and improve the outcomes. However, clinical studies are needed to evaluate these results in humans.

摘要

卵巢扭转是一种妇科急症,主要发生在女性生殖年龄,由于卵巢肿块或手术操作。本工作旨在探讨瘦素对大鼠卵巢缺血再灌注(IR)损伤的可能保护作用。Wistar 白化大鼠分为四组:1)对照组;2)卵巢 IR 组(OVIR);3)瘦素组 I [OVIR+瘦素(10μg/kg 体重,b.w.)];4)瘦素组 II(OVIR+瘦素(100μg/kg b.w.)]。测量血清雌二醇和抗苗勒管激素(AMH)水平。测定卵巢组织氧化应激和炎症标志物水平,并测定 Sirtuin 1(Sirt1)、核红细胞因子-2(Nrf2)、环氧化酶-2(COX-2)、核因子 kappa(NF-κB)、toll 样受体-4(TLR4)和半胱氨酸蛋白酶-3 的表达。OVIR 组血清雌二醇和 AMH 水平降低,COX-2、TLR4、caspase-3 和 NF-κB 表达增加,Sirt1 和 Nrf2 表达减少,两种剂量的外源性瘦素均可改善。瘦素通过调节 Sirt-1/Nrf2 和 TLR4/NF-kB/caspase-3 信号通路,剂量依赖性地减轻 OVIR 损伤的严重程度。因此,瘦素可作为一种辅助措施,预防卵巢损伤,改善结局。然而,需要进行临床研究来评估这些结果在人类中的应用。

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